5-112357674-T-C

Variant names:

• chr5-112357674-T-C
• rs379440
• NM_022140.5:c.100-50184A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022140.5(EPB41L4A):​c.100-50184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,280 control chromosomes in the GnomAD database, including 140 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 0.034 (140 hom., cov: 33)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 2 publications found

Genes affected

EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0345 (5253/152280) while in subpopulation NFE AF = 0.0484 (3292/68014). AF 95% confidence interval is 0.047. There are 140 homozygotes in GnomAd4. There are 2655 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 140 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.100-50184A>G		intron_variant	Intron 1 of 22	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.100-50184A>G		intron_variant	Intron 1 of 22	1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000305368.8	n.374-50184A>G		intron_variant	Intron 1 of 5	1
EPB41L4A	ENST00000512395.5	n.62+35049A>G		intron_variant	Intron 1 of 6	4

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5251 AN: 152162 Hom.: 140 Cov.: 33

Gnomad AFR AF: 0.00758

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0345 AC: 5253 AN: 152280 Hom.: 140 Cov.: 33 AF XY: 0.0357 AC XY: 2655 AN XY: 74462

African (AFR) AF: 0.00755 AC: 314 AN: 41566

American (AMR) AF: 0.0329 AC: 504 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4826

European-Finnish (FIN) AF: 0.0886 AC: 939 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3292 AN: 68014

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0423 Hom.: 352

Bravo AF: 0.0288

Asia WGS AF: 0.00924 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.83
PhyloP100		-0.14
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: rs379440; hg19: chr5-111693371;