Variant rs75674611 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_031844.3(HNRNPU):c.1743+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,610,250 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

HNRNPU
NM_031844.3 splice_region, intron

Scores

Splicing: ADA: 0.0001123

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0640

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:

HNRNPU (HGNC:):

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=-0.76).

BP6

Variant 1-244856720-C-A is Benign according to our data. Variant chr1-244856720-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 414106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-244856720-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00282 (429/152326) while in subpopulation AFR AF= 0.00994 (413/41560). AF 95% confidence interval is 0.00915. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPU	NM_031844.3 linkuse as main transcript	c.1743+8G>T		splice_region_variant, intron_variant		ENST00000640218.2	NP_114032.2	Q00839-1Q96BA7
HNRNPU	NM_004501.3 linkuse as main transcript	c.1686+8G>T		splice_region_variant, intron_variant			NP_004492.2	Q00839-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPU	ENST00000640218.2 linkuse as main transcript	c.1743+8G>T		splice_region_variant, intron_variant		1	NM_031844.3	ENSP00000491215.1		Q00839-1

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000638

AC:

158

AN:

247774

Hom.:

AF XY:

0.000455

AC XY:

AN XY:

133946

show subpopulations

Gnomad AFR exome

AF:

0.00958

Gnomad AMR exome

AF:

0.0000886

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000255

AC:

372

AN:

1457924

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

173

AN XY:

725122

show subpopulations

Gnomad4 AFR exome

AF:

0.00931

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000897

GnomAD4 genome

AF:

0.00282

AC:

429

AN:

152326

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00994

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00324

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 54

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 04, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.28

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0

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