rs200449454

Variant names:

• chr5-112165095-G-A
• rs200449454
• NM_022140.5:c.1956C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-112165095-G-A
• chr5-112165095-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022140.5(EPB41L4A):​c.1956C>T​(p.Ser652Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000233 in 1,457,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: EPB41L4A NM_022140.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.1956C>T	p.Ser652Ser	synonymous_variant	Exon 23 of 23	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.1956C>T	p.Ser652Ser	synonymous_variant	Exon 23 of 23	1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000509342.6	n.404C>T		non_coding_transcript_exon_variant	Exon 6 of 6	5
EPB41L4A	ENST00000507810.5	n.952+3644C>T		intron_variant	Intron 11 of 13	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000970 AC: 2 AN: 206122 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 112518

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1457204 Hom.: 0 Cov.: 30 AF XY: 0.0000290 AC XY: 21 AN XY: 725220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000307

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000113 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.2
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

Other links and lift over

dbSNP: rs200449454; hg19: chr5-111500792;