rs915171

Variant names:

• chr6-130863774-C-T
• rs915171
• NM_001431.4:c.2830-56G>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.2830-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,240,628 control chromosomes in the GnomAD database, including 49,353 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 0.30 (7042 hom., cov: 32)
  • Exomes 𝑓: 0.27 (42311 hom.)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 12 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 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.2830-56G>A		intron	N/A	NP_001422.1	O43491-1
	EPB41L2	NM_001350299.2		c.2986-56G>A		intron	N/A	NP_001337228.1	A0A994J5B1
	EPB41L2	NM_001350301.2		c.2887-56G>A		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.2830-56G>A		intron	N/A	ENSP00000338481.3	O43491-1
	EPB41L2	ENST00000528282.5	TSL:1	c.2056-56G>A		intron	N/A	ENSP00000434308.1	O43491-3
	EPB41L2	ENST00000392427.7	TSL:1	c.1834-56G>A		intron	N/A	ENSP00000376222.3	O43491-2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45588 AN: 151962 Hom.: 7033 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.274 AC: 297964 AN: 1088548 Hom.: 42311 AF XY: 0.275 AC XY: 153399 AN XY: 557238

African (AFR) AF: 0.361 AC: 9370 AN: 25944

American (AMR) AF: 0.342 AC: 14604 AN: 42674

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 4931 AN: 23346

East Asian (EAS) AF: 0.142 AC: 5361 AN: 37768

South Asian (SAS) AF: 0.322 AC: 24655 AN: 76612

European-Finnish (FIN) AF: 0.309 AC: 15988 AN: 51686

Middle Eastern (MID) AF: 0.202 AC: 1018 AN: 5034

European-Non Finnish (NFE) AF: 0.269 AC: 209369 AN: 777546

Other (OTH) AF: 0.264 AC: 12668 AN: 47938

GnomAD4 genome AF: 0.300 AC: 45626 AN: 152080 Hom.: 7042 Cov.: 32 AF XY: 0.300 AC XY: 22334 AN XY: 74326

African (AFR) AF: 0.362 AC: 15020 AN: 41470

American (AMR) AF: 0.313 AC: 4787 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.144 AC: 745 AN: 5172

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3277 AN: 10576

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18656 AN: 67976

Other (OTH) AF: 0.283 AC: 597 AN: 2106

Alfa AF: 0.281 Hom.: 8551

Bravo AF: 0.303

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.69
PhyloP100		-3.0
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: rs915171; hg19: chr6-131184914; COSMIC: COSV61354939;