Variant 5-179618141-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001257293.2(HNRNPH1):c.715+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,004 control chromosomes in the GnomAD database, including 56,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 5028 hom., cov: 32)

Exomes 𝑓: 0.25 ( 51418 hom. )

Consequence

HNRNPH1
NM_001257293.2 splice_donor_region, intron

Scores

Splicing: ADA: 0.00004657

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

Variant links:

Genes affected

HNRNPH1 (HGNC:5041): (heterogeneous nuclear ribonucleoprotein H1) This gene encodes a member of a subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA. These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some may shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNA and is very similar to the family member HNRPF. This gene may be associated with hereditary lymphedema type I. Alternatively spliced transcript variants have been described [provided by RefSeq, Mar 2012]

HNRNPH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-179618141-G-A is Benign according to our data. Variant chr5-179618141-G-A is described in ClinVar as [Benign]. Clinvar id is 1178581.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPH1	NM_001257293.2 linkuse as main transcript	c.715+4C>T		splice_donor_region_variant, intron_variant		ENST00000393432.9	NP_001244222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPH1	ENST00000393432.9 linkuse as main transcript	c.715+4C>T		splice_donor_region_variant, intron_variant		1	NM_001257293.2	ENSP00000377082	P4

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35465

AN:

151940

Hom.:

5030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.643

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.238

GnomAD3 exomes

AF:

0.303

AC:

76013

AN:

250852

Hom.:

14408

AF XY:

0.300

AC XY:

40623

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.644

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.248

AC:

362637

AN:

1460946

Hom.:

51418

Cov.:

AF XY:

0.252

AC XY:

183150

AN XY:

726726

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.471

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.233

AC:

35478

AN:

152058

Hom.:

5028

Cov.:

AF XY:

0.238

AC XY:

17662

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.643

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.238

Hom.:

6072

Bravo

AF:

0.249

Asia WGS

AF:

0.462

AC:

1610

AN:

3478

EpiCase

AF:

0.236

EpiControl

AF:

0.231

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0020

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.016

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