1-244855905-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_031844.3(HNRNPU):c.2166A>C(p.Gly722Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,611,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

HNRNPU
NM_031844.3 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.575

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-244855905-T-G is Benign according to our data. Variant chr1-244855905-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 532561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000171 (26/152010) while in subpopulation NFE AF = 0.000338 (23/67960). AF 95% confidence interval is 0.000231. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031844.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	NM_031844.3	MANE Select	c.2166A>C	p.Gly722Gly	splice_region synonymous	Exon 11 of 14	NP_114032.2
	HNRNPU	NM_004501.3		c.2109A>C	p.Gly703Gly	splice_region synonymous	Exon 11 of 14	NP_004492.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HNRNPU	ENST00000640218.2	TSL:1 MANE Select	c.2166A>C	p.Gly722Gly	splice_region synonymous	Exon 11 of 14	ENSP00000491215.1
HNRNPU	ENST00000444376.7	TSL:1	c.2109A>C	p.Gly703Gly	splice_region synonymous	Exon 11 of 14	ENSP00000393151.2
HNRNPU	ENST00000639628.2	TSL:1	c.1338A>C	p.Gly446Gly	splice_region synonymous	Exon 8 of 11	ENSP00000491340.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000151

AC:

AN:

250850

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000149

AC:

218

AN:

1459148

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

725656

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33416

American (AMR)

AF:

0.0000672

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000586

AC:

AN:

85342

European-Finnish (FIN)

AF:

0.000431

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000155

AC:

172

AN:

1110502

Other (OTH)

AF:

0.000166

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000171

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000782

Hom.:

Bravo

AF:

0.000125

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 54

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HNRNPU: BP4, BS2

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.57

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.35

Position offset: -1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over