rs112797967

Positions:

• chr11-124924689-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152722.5(HEPACAM):​c.427+39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,568,498 control chromosomes in the GnomAD database, including 646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (49 hom., cov: 32)
  • Exomes 𝑓: 0.027 (597 hom.)
• Consequence: HEPACAM NM_152722.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0900

Genes affected

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-124924689-C-T is Benign according to our data. Variant chr11-124924689-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0209 (3181/152238) while in subpopulation NFE AF= 0.0307 (2085/68006). AF 95% confidence interval is 0.0296. There are 49 homozygotes in gnomad4. There are 1487 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.427+39G>A		intron_variant		ENST00000298251.5	NP_689935.2
HEPACAM	NM_001411043.1	c.427+39G>A		intron_variant			NP_001397972.1
HEPACAM	XM_005271449.3	c.427+39G>A		intron_variant			XP_005271506.1
LOC107984406	XR_001748429.3	n.335-18711C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5	c.427+39G>A		intron_variant		1	NM_152722.5	ENSP00000298251.4
HEPACAM	ENST00000703807.1	c.427+39G>A		intron_variant				ENSP00000515485.1
HEPACAM	ENST00000528971.1	n.872G>A		non_coding_transcript_exon_variant	2/2	2
HEPACAM	ENST00000526273.1	n.199+39G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3184 AN: 152120 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00534

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00581

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0221 AC: 5498 AN: 248924 Hom.: 81 AF XY: 0.0224 AC XY: 3013 AN XY: 134802

Gnomad AFR exome AF: 0.00407

Gnomad AMR exome AF: 0.0208

Gnomad ASJ exome AF: 0.0249

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00585

Gnomad FIN exome AF: 0.0247

Gnomad NFE exome AF: 0.0318

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0267 AC: 37785 AN: 1416260 Hom.: 597 Cov.: 26 AF XY: 0.0262 AC XY: 18545 AN XY: 707146

Gnomad4 AFR exome AF: 0.00498

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0259

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00625

Gnomad4 FIN exome AF: 0.0261

Gnomad4 NFE exome AF: 0.0302

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0209 AC: 3181 AN: 152238 Hom.: 49 Cov.: 32 AF XY: 0.0200 AC XY: 1487 AN XY: 74436

Gnomad4 AFR AF: 0.00532

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0247 Hom.: 14

Bravo AF: 0.0206

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 04, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.50

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: rs112797967; hg19: chr11-124794585;