Variant 15-63712910-CAAA-CAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000443617.7(HERC1):c.4464-16_4464-15insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,372,942 control chromosomes in the GnomAD database, including 54 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 21 hom. )

Consequence

HERC1
ENST00000443617.7 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.01

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 -16 ACMG points.

BP6

Variant 15-63712910-C-CA is Benign according to our data. Variant chr15-63712910-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 445682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4 linkuse as main transcript	c.4464-16_4464-15insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
HERC1	ENST00000443617.7 linkuse as main transcript	c.4464-16_4464-15insT	splice_polypyrimidine_tract_variant, intron_variant	1	NM_003922.4	ENSP00000390158	P1
	ENST00000559303.2 linkuse as main transcript	n.288-546dup	intron_variant, non_coding_transcript_variant	5
HERC1	ENST00000561400.1 linkuse as main transcript	c.1416-16_1416-15insT	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000453937

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1863

AN:

143712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000298

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000220

Gnomad FIN

AF:

0.000337

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000184

Gnomad OTH

AF:

0.0142

GnomAD3 exomes

AF:

0.0111

AC:

1521

AN:

137116

Hom.:

AF XY:

0.00965

AC XY:

712

AN XY:

73780

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00799

Gnomad EAS exome

AF:

0.00579

Gnomad SAS exome

AF:

0.00733

Gnomad FIN exome

AF:

0.00867

Gnomad NFE exome

AF:

0.00514

Gnomad OTH exome

AF:

0.00994

GnomAD4 exome

AF:

0.00444

AC:

5458

AN:

1229130

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

2600

AN XY:

609674

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.00803

Gnomad4 ASJ exome

AF:

0.00455

Gnomad4 EAS exome

AF:

0.00333

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.00517

Gnomad4 NFE exome

AF:

0.00275

Gnomad4 OTH exome

AF:

0.00684

GnomAD4 genome

AF:

0.0130

AC:

1872

AN:

143812

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

858

AN XY:

69792

show subpopulations

Gnomad4 AFR

AF:

0.0456

Gnomad4 AMR

AF:

0.00254

Gnomad4 ASJ

AF:

0.000298

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000221

Gnomad4 FIN

AF:

0.000337

Gnomad4 NFE

AF:

0.000184

Gnomad4 OTH

AF:

0.0140

Bravo

AF:

0.0141

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 20, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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