chr6-130845317-T-C

Variant names:

• chr6-130845317-T-C
• rs4075265
• NM_001431.4:c.*6-4719A>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.*6-4719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,156 control chromosomes in the GnomAD database, including 47,484 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 0.78 (47484 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 5 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=-1.0).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	NM_001431.4	MANE Select	c.*6-4719A>G		intron	N/A	NP_001422.1
	EPB41L2	NM_001350299.2		c.*6-4719A>G		intron	N/A	NP_001337228.1
	EPB41L2	NM_001350301.2		c.*6-4719A>G		intron	N/A	NP_001337230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	ENST00000337057.8	TSL:1 MANE Select	c.*6-4719A>G		intron	N/A	ENSP00000338481.3
	EPB41L2	ENST00000528282.5	TSL:1	c.*6-4719A>G		intron	N/A	ENSP00000434308.1
	EPB41L2	ENST00000392427.7	TSL:1	c.*6-4719A>G		intron	N/A	ENSP00000376222.3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119025 AN: 152038 Hom.: 47430 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.783 AC: 119134 AN: 152156 Hom.: 47484 Cov.: 32 AF XY: 0.790 AC XY: 58768 AN XY: 74380

African (AFR) AF: 0.905 AC: 37598 AN: 41522

American (AMR) AF: 0.779 AC: 11917 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2149 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5163 AN: 5174

South Asian (SAS) AF: 0.853 AC: 4120 AN: 4828

European-Finnish (FIN) AF: 0.832 AC: 8789 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47093 AN: 67986

Other (OTH) AF: 0.730 AC: 1544 AN: 2114

Alfa AF: 0.725 Hom.: 8442

Bravo AF: 0.782

Asia WGS AF: 0.916 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		-0.23
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: rs4075265; hg19: chr6-131166457;