1-244864047-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_031844.3(HNRNPU):c.261G>A(p.Glu87Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,608,226 control chromosomes in the GnomAD database, including 50,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6618 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43738 hom. )

Consequence

HNRNPU
NM_031844.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.468

Publications

17 publications found

Variant links:

Genes affected

HNRNPU (HGNC:5048): (heterogeneous nuclear ribonucleoprotein U) This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with epileptic encephalopathy, early infantile, 54. A pseudogene of this gene has been identified on chromosome 14. [provided by RefSeq, Jun 2017]

HNRNPU Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 54
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

HNRNPU links:

ENSG00000273175 (HGNC:):

ENSG00000273175 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-244864047-C-T is Benign according to our data. Variant chr1-244864047-C-T is described in ClinVar as [Benign]. Clinvar id is 586025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.468 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPU	NM_031844.3 link	c.261G>A	p.Glu87Glu	synonymous_variant	Exon 1 of 14	ENST00000640218.2	NP_114032.2	Q00839-1Q96BA7
HNRNPU	NM_004501.3 link	c.261G>A	p.Glu87Glu	synonymous_variant	Exon 1 of 14		NP_004492.2	Q00839-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPU	ENST00000640218.2 link	c.261G>A	p.Glu87Glu	synonymous_variant	Exon 1 of 14	1	NM_031844.3	ENSP00000491215.1		Q00839-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43049

AN:

151940

Hom.:

6601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.271

AC:

63556

AN:

234182

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.239

AC:

348360

AN:

1456170

Hom.:

43738

Cov.:

AF XY:

0.237

AC XY:

171824

AN XY:

724006

show subpopulations

African (AFR)

AF:

0.376

AC:

12541

AN:

33356

American (AMR)

AF:

0.422

AC:

18584

AN:

43998

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6243

AN:

26008

East Asian (EAS)

AF:

0.140

AC:

5519

AN:

39460

South Asian (SAS)

AF:

0.223

AC:

19165

AN:

85796

European-Finnish (FIN)

AF:

0.338

AC:

17587

AN:

52100

Middle Eastern (MID)

AF:

0.214

AC:

1230

AN:

5758

European-Non Finnish (NFE)

AF:

0.228

AC:

252979

AN:

1109526

Other (OTH)

AF:

0.241

AC:

14512

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14886

29773

44659

59546

74432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8924

17848

26772

35696

44620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.283

AC:

43090

AN:

152056

Hom.:

6618

Cov.:

AF XY:

0.287

AC XY:

21342

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.370

AC:

15362

AN:

41484

American (AMR)

AF:

0.347

AC:

5313

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

811

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

900

AN:

5146

South Asian (SAS)

AF:

0.201

AC:

966

AN:

4814

European-Finnish (FIN)

AF:

0.351

AC:

3714

AN:

10582

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15215

AN:

67950

Other (OTH)

AF:

0.259

AC:

548

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1462

2923

4385

5846

7308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.240

Hom.:

1329

Bravo

AF:

0.290

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Developmental and epileptic encephalopathy, 54

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.47

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over