20-36182312-G-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012156.2(EPB41L1):​c.531G>A​(p.Pro177Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P177P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

EPB41L1
NM_012156.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

4 publications found
Variant links:
Genes affected
EPB41L1 (HGNC:3378): (erythrocyte membrane protein band 4.1 like 1) Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. The encoded protein binds and stabilizes D2 and D3 dopamine receptors at the neuronal plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
EPB41L1 Gene-Disease associations (from GenCC):
  • autosomal dominant non-syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • intellectual disability, autosomal dominant 11
    Inheritance: AD Classification: LIMITED Submitted by: G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPB41L1NM_012156.2 linkc.531G>A p.Pro177Pro synonymous_variant Exon 6 of 22 ENST00000338074.7 NP_036288.2 Q9H4G0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPB41L1ENST00000338074.7 linkc.531G>A p.Pro177Pro synonymous_variant Exon 6 of 22 1 NM_012156.2 ENSP00000337168.2 Q9H4G0-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000437
AC:
11
AN:
251448
AF XY:
0.0000147
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461784
Hom.:
0
Cov.:
31
AF XY:
0.0000261
AC XY:
19
AN XY:
727194
show subpopulations
African (AFR)
AF:
0.000388
AC:
13
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.0000348
AC:
3
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000198
AC:
22
AN:
1111918
Other (OTH)
AF:
0.0000662
AC:
4
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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:
0.000118
AC:
18
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74464
show subpopulations
African (AFR)
AF:
0.000433
AC:
18
AN:
41558
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.000102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
8.6
DANN
Benign
0.78
PhyloP100
-1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs139137163; hg19: chr20-34770234; COSMIC: COSV52433765; COSMIC: COSV52433765; API