6-130958535-G-A

Position:

• chr6-130958535-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001431.4(EPB41L2):​c.-14-2036C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 151,410 control chromosomes in the GnomAD database, including 194 homozygotes. 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: 𝑓 0.020 (194 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

Genes affected

EPB41L2 (HGNC:3379): (erythrocyte membrane protein band 4.1 like 2) Predicted to enable PH domain binding activity; cytoskeletal protein binding activity; and structural molecule activity. Involved in positive regulation of protein localization to cell cortex. Located in cell junction; nucleoplasm; and plasma membrane. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-14-2036C>T		intron_variant		ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-14-2036C>T		intron_variant		1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3006 AN: 151320 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00762

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0164

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0198 AC: 3000 AN: 151410 Hom.: 194 Cov.: 32 AF XY: 0.0212 AC XY: 1565 AN XY: 73866

Gnomad4 AFR AF: 0.00397

Gnomad4 AMR AF: 0.00768

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0172

Alfa AF: 0.0159 Hom.: 10

Bravo AF: 0.0202

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.83
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs10499178; hg19: chr6-131279675;