Variant chr15-63609286-G-A 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_003922.4(HERC1):c.14401-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,588,180 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 11 hom., cov: 33)

Exomes 𝑓: 0.012 ( 126 hom. )

Consequence

HERC1
NM_003922.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.06

Variant links:

Genes affected

HERC1 (HGNC:4867): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1) This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

HERC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-63609286-G-A is Benign according to our data. Variant chr15-63609286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1183226.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 = 0.00885 (1348/152342) while in subpopulation NFE AF= 0.015 (1022/68026). AF 95% confidence interval is 0.0143. There are 11 homozygotes in gnomad4. There are 610 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4 linkuse as main transcript	c.14401-20C>T		intron_variant		ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7 linkuse as main transcript	c.14401-20C>T		intron_variant		1	NM_003922.4	ENSP00000390158	P1

Frequencies

GnomAD3 genomes

AF:

0.00886

AC:

1348

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0150

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00951

AC:

2157

AN:

226852

Hom.:

AF XY:

0.00985

AC XY:

1208

AN XY:

122700

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00237

Gnomad FIN exome

AF:

0.00810

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0118

AC:

16921

AN:

1435838

Hom.:

126

Cov.:

AF XY:

0.0116

AC XY:

8273

AN XY:

710802

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00241

Gnomad4 FIN exome

AF:

0.00959

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.00992

GnomAD4 genome

AF:

0.00885

AC:

1348

AN:

152342

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00894

Gnomad4 NFE

AF:

0.0150

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00681

Hom.:

Bravo

AF:

0.00767

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.61

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