Variant rs141414233 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.6225+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 0.0073 in 1,581,242 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 43 hom. )

Consequence

HERC1
NM_003922.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.00009236

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.30

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:

(HGNC:):

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=-0.99).

BP6

Variant 15-63686355-G-A is Benign according to our data. Variant chr15-63686355-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63686355-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00544 (827/152024) while in subpopulation NFE AF= 0.00957 (651/67992). AF 95% confidence interval is 0.00897. There are 1 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC1	NM_003922.4 linkuse as main transcript	c.6225+4C>T		splice_donor_region_variant, intron_variant		ENST00000443617.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC1	ENST00000443617.7 linkuse as main transcript	c.6225+4C>T		splice_donor_region_variant, intron_variant		1	NM_003922.4	P1
	ENST00000559303.2 linkuse as main transcript	n.287+8036G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00544

AC:

827

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00956

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00527

AC:

1182

AN:

224164

Hom.:

AF XY:

0.00534

AC XY:

651

AN XY:

121810

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000761

Gnomad FIN exome

AF:

0.00230

Gnomad NFE exome

AF:

0.00892

Gnomad OTH exome

AF:

0.00600

GnomAD4 exome

AF:

0.00750

AC:

10722

AN:

1429218

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

5227

AN XY:

710032

show subpopulations

Gnomad4 AFR exome

AF:

0.00104

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00163

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000786

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.00896

Gnomad4 OTH exome

AF:

0.00639

GnomAD4 genome

AF:

0.00544

AC:

827

AN:

152024

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

361

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00393

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00152

Gnomad4 NFE

AF:

0.00957

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00411

Hom.:

Bravo

AF:

0.00584

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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	clinical testing	Invitae	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	HERC1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 27, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.0010

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000092

dbscSNV1_RF

Benign

0.16

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