15-63609577-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003922.4(HERC1):c.14401-311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,280 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.033 (98 hom., cov: 32)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-63609577-A-G is Benign according to our data. Variant chr15-63609577-A-G is described in ClinVar as [Benign]. Clinvar id is 1244404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0325 (4950/152280) while in subpopulation NFE AF= 0.0461 (3135/68010). AF 95% confidence interval is 0.0447. There are 98 homozygotes in gnomad4. There are 2466 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 98 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC1	NM_003922.4	c.14401-311T>C		intron_variant		ENST00000443617.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC1	ENST00000443617.7	c.14401-311T>C		intron_variant		1	NM_003922.4	P1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4952 AN: 152162 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.00710

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0325 AC: 4950 AN: 152280 Hom.: 98 Cov.: 32 AF XY: 0.0331 AC XY: 2466 AN XY: 74472

Gnomad4 AFR AF: 0.00710

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0497

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0376 Hom.: 8

Bravo AF: 0.0296

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.090
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs77075313; hg19: chr15-63901776;