rs11630290

chr15-63623587-C-T

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.13611+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 799,430 control chromosomes in the GnomAD database, including 19,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4048 hom., cov: 32)
  • Exomes 𝑓: 0.21 (15287 hom.)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.894

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=-0.65).
• BP6: Variant 15-63623587-C-T is Benign according to our data. Variant chr15-63623587-C-T is described in ClinVar as [Benign]. Clinvar id is 1235409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC1	NM_003922.4	c.13611+138G>A		intron_variant		ENST00000443617.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC1	ENST00000443617.7	c.13611+138G>A		intron_variant		1	NM_003922.4	P1
HERC1	ENST00000558324.1	c.*316+138G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34000 AN: 152024 Hom.: 4039 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.208 AC: 134861 AN: 647288 Hom.: 15287 AF XY: 0.205 AC XY: 69129 AN XY: 337976

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.224 AC: 34047 AN: 152142 Hom.: 4048 Cov.: 32 AF XY: 0.224 AC XY: 16625 AN XY: 74366

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.191

Alfa AF: 0.219 Hom.: 8240

Bravo AF: 0.226

Asia WGS AF: 0.0840 AC: 292 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 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.3
Dann	Benign	0.85

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: rs11630290; hg19: chr15-63915786;