rs115556036

Variant names:

• chr11-124920307-C-A
• rs115556036
• NM_152722.5:c.*831G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-124920307-C-A
• chr11-124920307-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152722.5(HEPACAM):​c.*831G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,289,320 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 30)
  • Exomes 𝑓: 0.00048 (6 hom.)
• Consequence: HEPACAM NM_152722.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.514
• Publications: 1 publications found

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]

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]

ENSG00000254943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-124920307-C-A is Benign according to our data. Variant chr11-124920307-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 878496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00541 (824/152196) while in subpopulation AFR AF = 0.019 (788/41520). AF 95% confidence interval is 0.0179. There are 7 homozygotes in GnomAd4. There are 361 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152722.5. 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
	HEPACAM	NM_152722.5	MANE Select	c.*831G>T		3_prime_UTR	Exon 7 of 7	NP_689935.2	Q14CZ8-1
	HEPN1	NM_001037558.4	MANE Select	c.*290C>A		3_prime_UTR	Exon 1 of 1	NP_001032647.2	Q6WQI6
	HEPACAM	NM_001411043.1		c.*831G>T		3_prime_UTR	Exon 7 of 7	NP_001397972.1	A0A994J4I1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.*831G>T		3_prime_UTR	Exon 7 of 7	ENSP00000298251.4	Q14CZ8-1
	HEPN1	ENST00000408930.7	TSL:6 MANE Select	c.*290C>A		3_prime_UTR	Exon 1 of 1	ENSP00000386143.4	Q6WQI6
	HEPACAM	ENST00000703807.1		c.*831G>T		3_prime_UTR	Exon 7 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 817 AN: 152078 Hom.: 7 Cov.: 30

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00384

GnomAD4 exome AF: 0.000482 AC: 548 AN: 1137124 Hom.: 6 Cov.: 15 AF XY: 0.000399 AC XY: 224 AN XY: 561006

African (AFR) AF: 0.0187 AC: 473 AN: 25292

American (AMR) AF: 0.000892 AC: 23 AN: 25774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19932

East Asian (EAS) AF: 0.00 AC: 0 AN: 33764

South Asian (SAS) AF: 0.0000462 AC: 3 AN: 64946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46140

Middle Eastern (MID) AF: 0.000800 AC: 4 AN: 5000

European-Non Finnish (NFE) AF: 0.00000346 AC: 3 AN: 867846

Other (OTH) AF: 0.000867 AC: 42 AN: 48430

GnomAD4 genome AF: 0.00541 AC: 824 AN: 152196 Hom.: 7 Cov.: 30 AF XY: 0.00485 AC XY: 361 AN XY: 74412

African (AFR) AF: 0.0190 AC: 788 AN: 41520

American (AMR) AF: 0.00144 AC: 22 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68008

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00612

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Megalencephalic leukoencephalopathy with subcortical cysts (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115556036; hg19: chr11-124790203;