chr6-130961070-T-C

Variant names:

• chr6-130961070-T-C
• rs6941712
• NM_001431.4:c.-14-4571A>G

Variant summary

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

The NM_001431.4(EPB41L2):​c.-14-4571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,126 control chromosomes in the GnomAD database, including 3,356 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 0.19 (3356 hom., cov: 33)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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.-14-4571A>G		intron	N/A	NP_001422.1
	EPB41L2	NM_001350299.2		c.-14-4571A>G		intron	N/A	NP_001337228.1
	EPB41L2	NM_001350301.2		c.-14-4571A>G		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.-14-4571A>G		intron	N/A	ENSP00000338481.3
	EPB41L2	ENST00000528282.5	TSL:1	c.-14-4571A>G		intron	N/A	ENSP00000434308.1
	EPB41L2	ENST00000392427.7	TSL:1	c.-14-4571A>G		intron	N/A	ENSP00000376222.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28533 AN: 152008 Hom.: 3349 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.188 AC: 28563 AN: 152126 Hom.: 3356 Cov.: 33 AF XY: 0.191 AC XY: 14178 AN XY: 74382

African (AFR) AF: 0.258 AC: 10706 AN: 41486

American (AMR) AF: 0.241 AC: 3682 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2446 AN: 5174

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4818

European-Finnish (FIN) AF: 0.145 AC: 1537 AN: 10586

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8316 AN: 67986

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.151 Hom.: 6767

Bravo AF: 0.198

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		0.60
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: rs6941712; hg19: chr6-131282210;