11-124919336-A-AAAAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001037558.4(HEPN1):c.-410_-407dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 199,830 control chromosomes in the GnomAD database, including 5,558 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4760 hom., cov: 25)
  • Exomes 𝑓: 0.15 (798 hom.)
• Consequence: HEPN1 NM_001037558.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.736

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 11-124919336-A-AAAAC is Benign according to our data. Variant chr11-124919336-A-AAAAC is described in ClinVar as [Benign]. Clinvar id is 303289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPN1	NM_001037558.4	c.-410_-407dup		5_prime_UTR_variant	1/1	ENST00000408930.7
HEPACAM	NM_152722.5	c.*1801_*1802insGTTT		3_prime_UTR_variant	7/7	ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-24059_335-24056dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPN1	ENST00000408930.7	c.-410_-407dup		5_prime_UTR_variant	1/1		NM_001037558.4	P1
HEPACAM	ENST00000298251.5	c.*1801_*1802insGTTT		3_prime_UTR_variant	7/7	1	NM_152722.5	P1
HEPACAM	ENST00000703807.1	c.*1801_*1802insGTTT		3_prime_UTR_variant	7/7

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36372 AN: 151834 Hom.: 4749 Cov.: 25

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.154 AC: 7378 AN: 47878 Hom.: 798 Cov.: 0 AF XY: 0.158 AC XY: 3755 AN XY: 23830

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.0861

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.0617

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.240 AC: 36419 AN: 151952 Hom.: 4760 Cov.: 25 AF XY: 0.240 AC XY: 17800 AN XY: 74308

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.210

Alfa AF: 0.228 Hom.: 434

Bravo AF: 0.231

Asia WGS AF: 0.201 AC: 695 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs560243987; hg19: chr11-124789232;