chr6-130934909-C-T

Variant names:

• chr6-130934909-C-T
• rs7748468
• NM_001431.4:c.706-8200G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001431.4(EPB41L2):​c.706-8200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,590 control chromosomes in the GnomAD database, including 49,398 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 0.80 (49398 hom., cov: 28)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	NM_001431.4	MANE Select	c.706-8200G>A		intron	N/A	NP_001422.1
	EPB41L2	NM_001350299.2		c.706-8200G>A		intron	N/A	NP_001337228.1
	EPB41L2	NM_001350301.2		c.706-8200G>A		intron	N/A	NP_001337230.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	ENST00000337057.8	TSL:1 MANE Select	c.706-8200G>A		intron	N/A	ENSP00000338481.3
	EPB41L2	ENST00000528282.5	TSL:1	c.706-8200G>A		intron	N/A	ENSP00000434308.1
	EPB41L2	ENST00000392427.7	TSL:1	c.706-8200G>A		intron	N/A	ENSP00000376222.3

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121347 AN: 151472 Hom.: 49334 Cov.: 28

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.801 AC: 121468 AN: 151590 Hom.: 49398 Cov.: 28 AF XY: 0.808 AC XY: 59790 AN XY: 74028

African (AFR) AF: 0.917 AC: 37925 AN: 41348

American (AMR) AF: 0.810 AC: 12316 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2189 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5175 AN: 5186

South Asian (SAS) AF: 0.866 AC: 4154 AN: 4798

European-Finnish (FIN) AF: 0.836 AC: 8705 AN: 10410

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48667 AN: 67872

Other (OTH) AF: 0.742 AC: 1559 AN: 2102

Alfa AF: 0.767 Hom.: 5873

Bravo AF: 0.802

Asia WGS AF: 0.924 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.90
DANN	Benign	0.53
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7748468; hg19: chr6-131256049;