11-124921088-G-C

Variant names:

• chr11-124921088-G-C
• rs192160991
• NM_152722.5:c.*50C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152722.5(HEPACAM):​c.*50C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,511,120 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (65 hom., cov: 32)
  • Exomes 𝑓: 0.017 (311 hom.)
• Consequence: HEPACAM NM_152722.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.25
• 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]

HEPACAM Gene-Disease associations (from GenCC):

• megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• megalencephalic leukoencephalopathy with subcortical cysts 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• macrocephaly-autism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• megalencephalic leukoencephalopathy with subcortical cysts

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000254943 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-124921088-G-C is Benign according to our data. Variant chr11-124921088-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

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.*50C>G		3_prime_UTR	Exon 7 of 7	NP_689935.2	Q14CZ8-1
	HEPACAM	NM_001411043.1		c.*50C>G		3_prime_UTR	Exon 7 of 7	NP_001397972.1	A0A994J4I1
	HEPACAM	NM_001441320.1		c.*50C>G		3_prime_UTR	Exon 7 of 7	NP_001428249.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM	ENST00000298251.5	TSL:1 MANE Select	c.*50C>G		3_prime_UTR	Exon 7 of 7	ENSP00000298251.4	Q14CZ8-1
	HEPACAM	ENST00000872129.1		c.*50C>G		3_prime_UTR	Exon 7 of 7	ENSP00000542188.1
	HEPACAM	ENST00000703807.1		c.*50C>G		3_prime_UTR	Exon 7 of 7	ENSP00000515485.1	A0A994J4I1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2214 AN: 152138 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0222 AC: 2513 AN: 113286 AF XY: 0.0184

Gnomad AFR exome AF: 0.00379

Gnomad AMR exome AF: 0.0742

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00281

Gnomad NFE exome AF: 0.0159

Gnomad OTH exome AF: 0.0172

GnomAD4 exome AF: 0.0168 AC: 22853 AN: 1358866 Hom.: 311 Cov.: 34 AF XY: 0.0162 AC XY: 10847 AN XY: 669694

African (AFR) AF: 0.00293 AC: 85 AN: 28998

American (AMR) AF: 0.0785 AC: 2633 AN: 33548

Ashkenazi Jewish (ASJ) AF: 0.00867 AC: 209 AN: 24116

East Asian (EAS) AF: 0.0000294 AC: 1 AN: 33996

South Asian (SAS) AF: 0.00184 AC: 142 AN: 77290

European-Finnish (FIN) AF: 0.00414 AC: 137 AN: 33076

Middle Eastern (MID) AF: 0.00175 AC: 7 AN: 3992

European-Non Finnish (NFE) AF: 0.0176 AC: 18766 AN: 1067272

Other (OTH) AF: 0.0154 AC: 873 AN: 56578

GnomAD4 genome AF: 0.0146 AC: 2218 AN: 152254 Hom.: 65 Cov.: 32 AF XY: 0.0147 AC XY: 1095 AN XY: 74440

African (AFR) AF: 0.00337 AC: 140 AN: 41566

American (AMR) AF: 0.0613 AC: 938 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1039 AN: 67992

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.0133 Hom.: 8

Bravo AF: 0.0180

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Megalencephalic leukoencephalopathy with subcortical cysts (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.68
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs192160991; hg19: chr11-124790984;