11-124919859-T-G

Variant names:

• chr11-124919859-T-G
• rs3802904
• ENST00000408930.7:c.109T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037558.4(HEPN1):​c.109T>G​(p.Trp37Gly) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W37R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HEPN1 NM_001037558.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

Genes affected

HEPN1 (HGNC:34400): (hepatocellular carcinoma, down-regulated 1) This gene is expressed predominantly in the liver. Transient transfection studies show the expression of this gene significantly inhibits cell growth, suggesting a role for this gene in apoptosis. Expression of this gene is down-regulated or lost in hepatocellular carcinomas (HCC), suggesting that loss of this gene is involved in carcinogenesis of hepatocytes (PMID:12971969). This gene maps to the 3'-noncoding region of the HEPACAM gene (GeneID:220296) on the antisense strand. [provided by RefSeq, Aug 2020]

HEPACAM (HGNC:26361): (hepatic and glial cell adhesion molecule) The protein encoded by this gene is a single-pass type I membrane protein that localizes to the cytoplasmic side of the cell membrane. The encoded protein acts as a homodimer and is involved in cell motility and cell-matrix interactions. The expression of this gene is downregulated or undetectable in many cancer cell lines, so this may be a tumor suppressor gene. [provided by RefSeq, Jul 2011]

LOC107984406 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05749789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.*1279A>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000298251.5	NP_689935.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPN1	ENST00000408930.7	c.109T>G	p.Trp37Gly	missense_variant	Exon 1 of 1	6		ENSP00000386143.4
HEPACAM	ENST00000298251	c.*1279A>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_152722.5	ENSP00000298251.4
HEPACAM	ENST00000703807	c.*1279A>C		3_prime_UTR_variant	Exon 7 of 7			ENSP00000515485.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.25
DANN	Benign	0.47
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.074
Sift4G	Benign	0.28	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.39		Gain of disorder (P = 0.0036);
MVP		0.030
MPC		0.055
ClinPred		0.021	T
GERP RS		0.86
Varity_R		0.31
gMVP		0.0051

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: rs3802904; hg19: chr11-124789755;