rs11636232
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1
The NM_004667.6(HERC2):c.11967G>A(p.Gln3989=) 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
NM_004667.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.859
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 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_single_submitter, 1 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 | UniProt |
---|---|---|---|---|---|---|---|
HERC2 | NM_004667.6 | c.11967G>A | p.Gln3989= | synonymous_variant | 78/93 | ENST00000261609.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.11967G>A | p.Gln3989= | synonymous_variant | 78/93 | 1 | NM_004667.6 | P1 | |
HERC2 | ENST00000650509.1 | c.3678G>A | p.Gln1226= | synonymous_variant, NMD_transcript_variant | 26/39 |
Frequencies
GnomAD3 genomes ? AF: 0.250 AC: 37948AN: 151960Hom.: 7247 Cov.: 31
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GnomAD3 exomes AF: 0.249 AC: 62555AN: 251456Hom.: 12422 AF XY: 0.245 AC XY: 33275AN XY: 135902
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GnomAD4 exome AF: 0.346 AC: 506003AN: 1461644Hom.: 102947 Cov.: 44 AF XY: 0.336 AC XY: 244364AN XY: 727142
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GnomAD4 genome ? AF: 0.249 AC: 37942AN: 152078Hom.: 7247 Cov.: 31 AF XY: 0.243 AC XY: 18069AN XY: 74326
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at