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GeneBe

20-36182336-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_012156.2(EPB41L1):c.555A>G(p.Glu185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,614,070 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 45 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 42 hom. )

Consequence

EPB41L1
NM_012156.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.56
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-36182336-A-G is Benign according to our data. Variant chr20-36182336-A-G is described in ClinVar as [Benign]. Clinvar id is 129001.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.56 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2042/152318) while in subpopulation AFR AF= 0.0469 (1950/41556). AF 95% confidence interval is 0.0452. There are 45 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 2030 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPB41L1NM_012156.2 linkuse as main transcriptc.555A>G p.Glu185= synonymous_variant 6/22 ENST00000338074.7
LOC124904892XR_007067571.1 linkuse as main transcriptn.265-688T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPB41L1ENST00000338074.7 linkuse as main transcriptc.555A>G p.Glu185= synonymous_variant 6/221 NM_012156.2 P5Q9H4G0-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0133
AC:
2030
AN:
152200
Hom.:
43
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0468
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00438
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:
0.000103
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00324
AC:
815
AN:
251416
Hom.:
10
AF XY:
0.00229
AC XY:
311
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.0456
Gnomad AMR exome
AF:
0.00165
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.00136
AC:
1988
AN:
1461752
Hom.:
42
Cov.:
31
AF XY:
0.00111
AC XY:
806
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0500
Gnomad4 AMR exome
AF:
0.00190
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00296
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0134
AC:
2042
AN:
152318
Hom.:
45
Cov.:
32
AF XY:
0.0130
AC XY:
966
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0469
Gnomad4 AMR
AF:
0.00438
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00601
Hom.:
9
Bravo
AF:
0.0154
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
11
Dann
Benign
0.89

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: rs116334224; hg19: chr20-34770258; API