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GeneBe

5-112169066-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_022140.5(EPB41L4A):c.1779G>A(p.Ser593=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

EPB41L4A
NM_022140.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.97
Variant links:
Genes affected
EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-112169066-C-T is Benign according to our data. Variant chr5-112169066-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 752359.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=-3.97 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPB41L4ANM_022140.5 linkuse as main transcriptc.1779G>A p.Ser593= synonymous_variant 21/23 ENST00000261486.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPB41L4AENST00000261486.6 linkuse as main transcriptc.1779G>A p.Ser593= synonymous_variant 21/231 NM_022140.5 P1
EPB41L4AENST00000507810.5 linkuse as main transcriptn.799G>A non_coding_transcript_exon_variant 10/142
EPB41L4AENST00000509342.6 linkuse as main transcriptn.227G>A non_coding_transcript_exon_variant 4/65

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152086
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000387
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000561
AC:
14
AN:
249574
Hom.:
0
AF XY:
0.0000591
AC XY:
8
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.000387
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.0000413
AC XY:
30
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000197
AC:
30
AN:
152086
Hom.:
1
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.000387
Gnomad4 AMR
AF:
0.000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000232
Hom.:
0
Bravo
AF:
0.000230
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJun 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
1.8
Dann
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs771013845; hg19: chr5-111504763; COSMIC: COSV54870293; COSMIC: COSV54870293; API