rs12414281

Variant names:

• chr10-67955812-G-A
• rs12414281
• NM_015601.4:c.2026-682C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-67955812-G-A
• chr10-67955812-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015601.4(HERC4):​c.2026-682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,112 control chromosomes in the GnomAD database, including 961 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (961 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: HERC4 NM_015601.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• Publications: 1 publications found

Genes affected

HERC4 (HGNC:24521): (HECT and RLD domain containing E3 ubiquitin protein ligase 4) HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERC4	NM_015601.4	c.2026-682C>T		intron_variant	Intron 17 of 24	ENST00000373700.9	NP_056416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERC4	ENST00000373700.9	c.2026-682C>T		intron_variant	Intron 17 of 24	1	NM_015601.4	ENSP00000362804.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16810 AN: 151984 Hom.: 961 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.111 AC: 16825 AN: 152102 Hom.: 961 Cov.: 32 AF XY: 0.111 AC XY: 8223 AN XY: 74356

African (AFR) AF: 0.0735 AC: 3050 AN: 41504

American (AMR) AF: 0.140 AC: 2136 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.130 AC: 671 AN: 5180

South Asian (SAS) AF: 0.148 AC: 711 AN: 4814

European-Finnish (FIN) AF: 0.0989 AC: 1048 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8423 AN: 67964

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.0940 Hom.: 312

Bravo AF: 0.110

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.65
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12414281; hg19: chr10-69715569;