Menu
GeneBe

5-112184063-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_022140.5(EPB41L4A):c.1575A>G(p.Lys525=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,614,074 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 19 hom., cov: 32)
Exomes 𝑓: 0.0038 ( 179 hom. )

Consequence

EPB41L4A
NM_022140.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28
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 -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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-112184063-T-C is Benign according to our data. Variant chr5-112184063-T-C is described in ClinVar as [Benign]. Clinvar id is 787980.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=1.28 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPB41L4ANM_022140.5 linkuse as main transcriptc.1575A>G p.Lys525= synonymous_variant 18/23 ENST00000261486.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPB41L4AENST00000261486.6 linkuse as main transcriptc.1575A>G p.Lys525= synonymous_variant 18/231 NM_022140.5 P1
EPB41L4AENST00000507810.5 linkuse as main transcriptn.595A>G non_coding_transcript_exon_variant 7/142
EPB41L4AENST00000515047.5 linkuse as main transcriptn.395A>G non_coding_transcript_exon_variant 5/73

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00613
AC:
933
AN:
152188
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0134
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00808
Gnomad SAS
AF:
0.0630
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00833
AC:
2079
AN:
249550
Hom.:
52
AF XY:
0.0103
AC XY:
1392
AN XY:
135386
show subpopulations
Gnomad AFR exome
AF:
0.0134
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00818
Gnomad SAS exome
AF:
0.0540
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000168
Gnomad OTH exome
AF:
0.00594
GnomAD4 exome
AF:
0.00383
AC:
5605
AN:
1461768
Hom.:
179
Cov.:
34
AF XY:
0.00532
AC XY:
3869
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0123
Gnomad4 AMR exome
AF:
0.000648
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00577
Gnomad4 SAS exome
AF:
0.0521
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000639
Gnomad4 OTH exome
AF:
0.00581
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00612
AC:
932
AN:
152306
Hom.:
19
Cov.:
32
AF XY:
0.00710
AC XY:
529
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0134
Gnomad4 AMR
AF:
0.00105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00791
Gnomad4 SAS
AF:
0.0627
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00221
Hom.:
2
Bravo
AF:
0.00466
Asia WGS
AF:
0.0510
AC:
176
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

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
-0.53
Cadd
Benign
5.3
Dann
Benign
0.61

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: rs111958355; hg19: chr5-111519760; API