rs112797967

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0900

Publications

3 publications found
Variant links:
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: Ambry Genetics, ClinGen, 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

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
HEPACAMNM_152722.5 linkc.427+39G>A intron_variant Intron 2 of 6 ENST00000298251.5 NP_689935.2 Q14CZ8-1
HEPACAMNM_001411043.1 linkc.427+39G>A intron_variant Intron 2 of 6 NP_001397972.1
HEPACAMNM_001441320.1 linkc.427+39G>A intron_variant Intron 2 of 6 NP_001428249.1
LOC107984406XR_001748429.3 linkn.335-18711C>T intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HEPACAMENST00000298251.5 linkc.427+39G>A intron_variant Intron 2 of 6 1 NM_152722.5 ENSP00000298251.4 Q14CZ8-1

Frequencies

GnomAD3 genomes
AF:
0.0209
AC:
3184
AN:
152120
Hom.:
49
Cov.:
32
show subpopulations
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
GnomAD2 exomes
AF:
0.0221
AC:
5498
AN:
248924
AF XY:
0.0224
show subpopulations
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 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
show subpopulations
African (AFR)
AF:
0.00498
AC:
162
AN:
32522
American (AMR)
AF:
0.0218
AC:
973
AN:
44662
Ashkenazi Jewish (ASJ)
AF:
0.0259
AC:
670
AN:
25822
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39476
South Asian (SAS)
AF:
0.00625
AC:
533
AN:
85264
European-Finnish (FIN)
AF:
0.0261
AC:
1391
AN:
53288
Middle Eastern (MID)
AF:
0.0281
AC:
160
AN:
5684
European-Non Finnish (NFE)
AF:
0.0302
AC:
32381
AN:
1070656
Other (OTH)
AF:
0.0257
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

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1144
2288
3432
4576
5720
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0209
AC:
3181
AN:
152238
Hom.:
49
Cov.:
32
AF XY:
0.0200
AC XY:
1487
AN XY:
74436
show subpopulations
African (AFR)
AF:
0.00532
AC:
221
AN:
41544
American (AMR)
AF:
0.0225
AC:
344
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.0282
AC:
98
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5176
South Asian (SAS)
AF:
0.00560
AC:
27
AN:
4818
European-Finnish (FIN)
AF:
0.0248
AC:
263
AN:
10610
Middle Eastern (MID)
AF:
0.0238
AC:
7
AN:
294
European-Non Finnish (NFE)
AF:
0.0307
AC:
2085
AN:
68006
Other (OTH)
AF:
0.0298
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

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
40
80
120
160
200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.0
DANN
Benign
0.50
PhyloP100
0.090
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

Publications

Other links and lift over

dbSNP: rs112797967; hg19: chr11-124794585; API