Variant 1-244856718-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000640218.2(HNRNPU):c.1743+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,609,452 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 153 hom. )

Consequence

HNRNPU
ENST00000640218.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.641

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-244856718-T-G is Benign according to our data. Variant chr1-244856718-T-G is described in ClinVar as [Benign]. Clinvar id is 414097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPU	NM_031844.3 linkuse as main transcript	c.1743+10A>C		intron_variant		ENST00000640218.2	NP_114032.2
HNRNPU	NM_004501.3 linkuse as main transcript	c.1686+10A>C		intron_variant			NP_004492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPU	ENST00000640218.2 linkuse as main transcript	c.1743+10A>C		intron_variant		1	NM_031844.3	ENSP00000491215	P3	Q00839-1

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

514

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00728

AC:

1798

AN:

247130

Hom.:

AF XY:

0.00676

AC XY:

903

AN XY:

133648

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.000813

Gnomad EAS exome

AF:

0.0896

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.00339

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00261

AC:

3805

AN:

1457102

Hom.:

153

Cov.:

AF XY:

0.00259

AC XY:

1880

AN XY:

724676

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0000459

Gnomad4 ASJ exome

AF:

0.000579

Gnomad4 EAS exome

AF:

0.0792

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00337

AC:

514

AN:

152350

Hom.:

Cov.:

AF XY:

0.00412

AC XY:

307

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.0851

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000405

Hom.:

Bravo

AF:

0.00392

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 18, 2017	- -

Developmental and epileptic encephalopathy, 54

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.2

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over