15-63712910-CAAA-CAA

Position:

• chr15-63712910-CAAA-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP6_Very_Strong BS1

The NM_003922.4(HERC1):​c.4464-16delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,399,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (0 hom.)
• Consequence: HERC1 NM_003922.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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]

ENSG00000259589 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-63712910-CA-C is Benign according to our data. Variant chr15-63712910-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000904 (13/143736) while in subpopulation NFE AF= 0.000154 (10/65094). AF 95% confidence interval is 0.0000824. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC1	NM_003922.4	c.4464-16delT		intron_variant		ENST00000443617.7	NP_003913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC1	ENST00000443617.7	c.4464-16delT		intron_variant		1	NM_003922.4	ENSP00000390158.2
HERC1	ENST00000561400.1	c.1416-16delT		intron_variant		2		ENSP00000453937.1
ENSG00000259589	ENST00000559303.2	n.288-546delA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000904 AC: 13 AN: 143736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000225

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00988 AC: 1355 AN: 137116 Hom.: 0 AF XY: 0.0102 AC XY: 753 AN XY: 73780

Gnomad AFR exome AF: 0.00562

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00755

Gnomad SAS exome AF: 0.00869

Gnomad FIN exome AF: 0.00591

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00962

GnomAD4 exome AF: 0.00141 AC: 1769 AN: 1255544 Hom.: 0 Cov.: 31 AF XY: 0.00149 AC XY: 928 AN XY: 622390

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.00571

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.00229

Gnomad4 FIN exome AF: 0.00313

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.0000904 AC: 13 AN: 143736 Hom.: 0 Cov.: 32 AF XY: 0.000100 AC XY: 7 AN XY: 69684

Gnomad4 AFR AF: 0.0000255

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000225

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Mar 08, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2019	- -

Computational scores

Source: dbNSFP v4.3

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: rs369792267; hg19: chr15-64005109;