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GeneBe

5-112195690-A-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_022140.5(EPB41L4A):c.1395T>A(p.Gly465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00822 in 1,613,490 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0085 ( 57 hom. )

Consequence

EPB41L4A
NM_022140.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00600
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 Benign. Variant got -11 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=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-112195690-A-T is Benign according to our data. Variant chr5-112195690-A-T is described in ClinVar as [Benign]. Clinvar id is 714299.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=-0.006 with no splicing effect.
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 Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPB41L4ANM_022140.5 linkuse as main transcriptc.1395T>A p.Gly465= synonymous_variant 16/23 ENST00000261486.6
LOC124901044XR_007058902.1 linkuse as main transcriptn.63+1031A>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPB41L4AENST00000261486.6 linkuse as main transcriptc.1395T>A p.Gly465= synonymous_variant 16/231 NM_022140.5 P1
ENST00000506875.1 linkuse as main transcriptn.96+1031A>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00581
AC:
883
AN:
152066
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00254
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00406
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00500
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00950
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00572
AC:
1425
AN:
249088
Hom.:
3
AF XY:
0.00558
AC XY:
754
AN XY:
135144
show subpopulations
Gnomad AFR exome
AF:
0.00187
Gnomad AMR exome
AF:
0.00241
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00530
Gnomad NFE exome
AF:
0.0100
Gnomad OTH exome
AF:
0.00663
GnomAD4 exome
AF:
0.00847
AC:
12384
AN:
1461306
Hom.:
57
Cov.:
30
AF XY:
0.00821
AC XY:
5968
AN XY:
726964
show subpopulations
Gnomad4 AFR exome
AF:
0.00138
Gnomad4 AMR exome
AF:
0.00295
Gnomad4 ASJ exome
AF:
0.00126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00665
Gnomad4 NFE exome
AF:
0.0102
Gnomad4 OTH exome
AF:
0.00754
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00580
AC:
883
AN:
152184
Hom.:
1
Cov.:
32
AF XY:
0.00528
AC XY:
393
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00253
Gnomad4 AMR
AF:
0.00406
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00500
Gnomad4 NFE
AF:
0.00950
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00794
Hom.:
1
Bravo
AF:
0.00569
EpiCase
AF:
0.00769
EpiControl
AF:
0.00848

ClinVar

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

Submissions by phenotype

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
-0.58
Cadd
Benign
9.9
Dann
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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: rs149373122; hg19: chr5-111531387; API