rs2972011

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-88698125-A-C
• chr4-88698125-A-G
• chr4-88698125-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014606.3(HERC3):​c.2658-5973A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: HERC3 NM_014606.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014606.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC3	NM_014606.3	MANE Select	c.2658-5973A>C		intron	N/A	NP_055421.1	Q15034-1
	HERC3	NM_001375480.1		c.2655-5973A>C		intron	N/A	NP_001362409.1
	HERC3	NM_001375478.1		c.2634-5973A>C		intron	N/A	NP_001362407.1	H0Y8G9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC3	ENST00000402738.6	TSL:1 MANE Select	c.2658-5973A>C		intron	N/A	ENSP00000385684.1	Q15034-1
	HERC3	ENST00000512194.2	TSL:5	c.2634-5973A>C		intron	N/A	ENSP00000421021.2	H0Y8G9
	HERC3	ENST00000950980.1		c.2661-5973A>C		intron	N/A	ENSP00000621039.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 11768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-1.4
PromoterAI		0.032	Neutral

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: rs2972011; hg19: chr4-89619276;