rs140731421

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_012156.2(EPB41L1):​c.111C>T​(p.His37His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,974 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

EPB41L1
NM_012156.2 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.919
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 20-36173888-C-T is Benign according to our data. Variant chr20-36173888-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 736255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.919 with no splicing effect.
BS2
High AC in GnomAd4 at 150 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPB41L1NM_012156.2 linkc.111C>T p.His37His synonymous_variant Exon 2 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.111C>T p.His37His synonymous_variant Exon 2 of 22 1 NM_012156.2 ENSP00000337168.2 Q9H4G0-1

Frequencies

GnomAD3 genomes
AF:
0.000992
AC:
151
AN:
152166
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00196
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000880
AC:
220
AN:
250042
Hom.:
0
AF XY:
0.000879
AC XY:
119
AN XY:
135338
show subpopulations
Gnomad AFR exome
AF:
0.000558
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000325
Gnomad NFE exome
AF:
0.00177
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.00175
AC:
2559
AN:
1461690
Hom.:
5
Cov.:
32
AF XY:
0.00173
AC XY:
1256
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000375
Gnomad4 NFE exome
AF:
0.00208
Gnomad4 OTH exome
AF:
0.00359
GnomAD4 genome
AF:
0.000985
AC:
150
AN:
152284
Hom.:
1
Cov.:
32
AF XY:
0.000833
AC XY:
62
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00194
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00147
Hom.:
0
Bravo
AF:
0.000929
EpiCase
AF:
0.00180
EpiControl
AF:
0.000653

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
Mar 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

EPB41L1: BS1, BS2 -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Dec 18, 2017
Genetic Services Laboratory, University of Chicago
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
-0.39
CADD
Benign
14
DANN
Benign
0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140731421; hg19: chr20-34761810; COSMIC: COSV52434417; API