6-131011522-A-G

Variant names:

• chr6-131011522-A-G
• rs6907809
• NM_001431.4:c.-15+51633T>C

Variant summary

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

The NM_001431.4(EPB41L2):​c.-15+51633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,152 control chromosomes in the GnomAD database, including 7,359 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 (7359 hom., cov: 31)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 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.-15+51633T>C		intron	N/A	NP_001422.1	O43491-1
	EPB41L2	NM_001350301.2		c.-15+51633T>C		intron	N/A	NP_001337230.1
	EPB41L2	NM_001350303.2		c.-15+51633T>C		intron	N/A	NP_001337232.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	ENST00000337057.8	TSL:1 MANE Select	c.-15+51633T>C		intron	N/A	ENSP00000338481.3	O43491-1
	EPB41L2	ENST00000392427.7	TSL:1	c.-15+51633T>C		intron	N/A	ENSP00000376222.3	O43491-2
	EPB41L2	ENST00000922900.1		c.-15+51633T>C		intron	N/A	ENSP00000592959.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45183 AN: 152034 Hom.: 7339 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.297 AC: 45242 AN: 152152 Hom.: 7359 Cov.: 31 AF XY: 0.299 AC XY: 22250 AN XY: 74358

African (AFR) AF: 0.419 AC: 17381 AN: 41480

American (AMR) AF: 0.247 AC: 3777 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3466

East Asian (EAS) AF: 0.450 AC: 2326 AN: 5174

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4828

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10590

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15399 AN: 68006

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.170 Hom.: 394

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		0.73
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: rs6907809; hg19: chr6-131332662;