15-63608914-A-G

Position:

• chr15-63608914-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003922.4(HERC1):​c.*167T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.169 in 522,252 control chromosomes in the GnomAD database, including 8,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2227 hom., cov: 33)
  • Exomes 𝑓: 0.17 (6481 hom.)
• Consequence: HERC1 NM_003922.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.19

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-63608914-A-G is Benign according to our data. Variant chr15-63608914-A-G is described in ClinVar as [Benign]. Clinvar id is 1221333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4	c.*167T>C		3_prime_UTR_variant	78/78	ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7	c.*167T>C		3_prime_UTR_variant	78/78	1	NM_003922.4	ENSP00000390158	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24050 AN: 152160 Hom.: 2231 Cov.: 33

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.174 AC: 64328 AN: 369974 Hom.: 6481 Cov.: 6 AF XY: 0.175 AC XY: 32778 AN XY: 186912

Gnomad4 AFR exome AF: 0.0885

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.000436

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.158 AC: 24040 AN: 152278 Hom.: 2227 Cov.: 33 AF XY: 0.157 AC XY: 11720 AN XY: 74438

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.164

Alfa AF: 0.151 Hom.: 462

Bravo AF: 0.142

Asia WGS AF: 0.0870 AC: 301 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.36
CADD	Benign	16
DANN	Benign	0.88

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: rs1131647; hg19: chr15-63901113;