rs112797967
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
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
NM_152722.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0900
Publications
3 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 disabilityInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
- megalencephalic leukoencephalopathy with subcortical cysts 2AInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
- macrocephaly-autism syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- megalencephalic leukoencephalopathy with subcortical cystsInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 49 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HEPACAM | NM_152722.5 | c.427+39G>A | intron_variant | Intron 2 of 6 | ENST00000298251.5 | NP_689935.2 | ||
HEPACAM | NM_001411043.1 | c.427+39G>A | intron_variant | Intron 2 of 6 | NP_001397972.1 | |||
HEPACAM | NM_001441320.1 | c.427+39G>A | intron_variant | Intron 2 of 6 | NP_001428249.1 | |||
LOC107984406 | XR_001748429.3 | n.335-18711C>T | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0209 AC: 3184AN: 152120Hom.: 49 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3184
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0221 AC: 5498AN: 248924 AF XY: 0.0224 show subpopulations
GnomAD2 exomes
AF:
AC:
5498
AN:
248924
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0267 AC: 37785AN: 1416260Hom.: 597 Cov.: 26 AF XY: 0.0262 AC XY: 18545AN XY: 707146 show subpopulations
GnomAD4 exome
AF:
AC:
37785
AN:
1416260
Hom.:
Cov.:
26
AF XY:
AC XY:
18545
AN XY:
707146
show subpopulations
African (AFR)
AF:
AC:
162
AN:
32522
American (AMR)
AF:
AC:
973
AN:
44662
Ashkenazi Jewish (ASJ)
AF:
AC:
670
AN:
25822
East Asian (EAS)
AF:
AC:
0
AN:
39476
South Asian (SAS)
AF:
AC:
533
AN:
85264
European-Finnish (FIN)
AF:
AC:
1391
AN:
53288
Middle Eastern (MID)
AF:
AC:
160
AN:
5684
European-Non Finnish (NFE)
AF:
AC:
32381
AN:
1070656
Other (OTH)
AF:
AC:
1515
AN:
58886
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
2067
4134
6202
8269
10336
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0209 AC: 3181AN: 152238Hom.: 49 Cov.: 32 AF XY: 0.0200 AC XY: 1487AN XY: 74436 show subpopulations
GnomAD4 genome
AF:
AC:
3181
AN:
152238
Hom.:
Cov.:
32
AF XY:
AC XY:
1487
AN XY:
74436
show subpopulations
African (AFR)
AF:
AC:
221
AN:
41544
American (AMR)
AF:
AC:
344
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
98
AN:
3472
East Asian (EAS)
AF:
AC:
1
AN:
5176
South Asian (SAS)
AF:
AC:
27
AN:
4818
European-Finnish (FIN)
AF:
AC:
263
AN:
10610
Middle Eastern (MID)
AF:
AC:
7
AN:
294
European-Non Finnish (NFE)
AF:
AC:
2085
AN:
68006
Other (OTH)
AF:
AC:
63
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
145
290
434
579
724
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
20
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Apr 04, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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