Variant rs11636232 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004667.6(HERC2):c.11967G>A(p.Gln3989Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,613,722 control chromosomes in the GnomAD database, including 110,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 7247 hom., cov: 31)

Exomes 𝑓: 0.35 ( 102947 hom. )

Consequence

HERC2
NM_004667.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.859

Variant links:

Genes affected

HERC2 (HGNC:4868): (HECT and RLD domain containing E3 ubiquitin protein ligase 2) This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]

HERC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 15-28141480-C-T is Benign according to our data. Variant chr15-28141480-C-T is described in ClinVar as [Benign]. Clinvar id is 1224285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.859 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC2	NM_004667.6 link	c.11967G>A	p.Gln3989Gln	synonymous_variant	78/93	ENST00000261609.13	NP_004658.3	O95714A8KAQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC2	ENST00000261609.13 link	c.11967G>A	p.Gln3989Gln	synonymous_variant	78/93	1	NM_004667.6	ENSP00000261609.8		O95714
HERC2	ENST00000650509.1 link	n.3678G>A		non_coding_transcript_exon_variant	26/39			ENSP00000496936.1		A0A3B3IRP6

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37948

AN:

151960

Hom.:

7247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0670

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.249

AC:

62555

AN:

251456

Hom.:

12422

AF XY:

0.245

AC XY:

33275

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0624

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.346

AC:

506003

AN:

1461644

Hom.:

102947

Cov.:

AF XY:

0.336

AC XY:

244364

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.0749

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0285

Gnomad4 FIN exome

AF:

0.503

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.249

AC:

37942

AN:

152078

Hom.:

7247

Cov.:

AF XY:

0.243

AC XY:

18069

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0668

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.492

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.322

Hom.:

14137

Bravo

AF:

0.213

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	May 13, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

2.3

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over