chr15-63609447-G-A

Position:

• chr15-63609447-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003922.4(HERC1):​c.14401-181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,226 control chromosomes in the GnomAD database, including 52,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.81 (52360 hom., cov: 33)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-63609447-G-A is Benign according to our data. Variant chr15-63609447-G-A is described in ClinVar as [Benign]. Clinvar id is 1235379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4	c.14401-181C>T		intron_variant		ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7	c.14401-181C>T		intron_variant		1	NM_003922.4	ENSP00000390158	P1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123846 AN: 152108 Hom.: 52305 Cov.: 33

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.814 AC: 123960 AN: 152226 Hom.: 52360 Cov.: 33 AF XY: 0.802 AC XY: 59698 AN XY: 74432

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.808

Alfa AF: 0.851 Hom.: 7692

Bravo AF: 0.804

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.70

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: rs4984252; hg19: chr15-63901646;