chr15-63612081-C-G

Position:

• chr15-63612081-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003922.4(HERC1):​c.14400+170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,178 control chromosomes in the GnomAD database, including 2,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2219 hom., cov: 32)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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=-1.03).
• BP6: Variant 15-63612081-C-G is Benign according to our data. Variant chr15-63612081-C-G is described in ClinVar as [Benign]. Clinvar id is 1276914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4	c.14400+170G>C		intron_variant		ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7	c.14400+170G>C		intron_variant		1	NM_003922.4	ENSP00000390158	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23766 AN: 152060 Hom.: 2223 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.156 AC: 23756 AN: 152178 Hom.: 2219 Cov.: 32 AF XY: 0.156 AC XY: 11592 AN XY: 74408

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.165

Alfa AF: 0.108 Hom.: 205

Bravo AF: 0.139

Asia WGS AF: 0.0820 AC: 286 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	-1.0
CADD	Benign	1.0
DANN	Benign	0.16

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: rs62012818; hg19: chr15-63904280;