NM_014606.3:c.2658-5973A>G

Variant names:

• chr4-88698125-A-G
• rs2972011
• NM_014606.3:c.2658-5973A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014606.3(HERC3):​c.2658-5973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,732 control chromosomes in the GnomAD database, including 11,063 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 0.36 (11063 hom., cov: 31)
• Consequence: HERC3 NM_014606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

HERC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERC3	NM_014606.3	c.2658-5973A>G		intron_variant	Intron 23 of 25	ENST00000402738.6	NP_055421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERC3	ENST00000402738.6	c.2658-5973A>G		intron_variant	Intron 23 of 25	1	NM_014606.3	ENSP00000385684.1
HERC3	ENST00000264345.7	c.2658-5973A>G		intron_variant	Intron 21 of 23	1
HERC3	ENST00000512194.2	c.2634-5973A>G		intron_variant	Intron 23 of 25	5		ENSP00000421021.2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55202 AN: 151614 Hom.: 11033 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55274 AN: 151732 Hom.: 11063 Cov.: 31 AF XY: 0.374 AC XY: 27721 AN XY: 74158

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.335

Alfa AF: 0.331 Hom.: 2695

Bravo AF: 0.361

Asia WGS AF: 0.574 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.49

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: rs2972011; hg19: chr4-89619276;