rs7858370

Variant names:

• chr9-109210740-G-A
• rs7858370
• NM_019114.5:c.1753-2691C>T

Variant summary

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

The NM_019114.5(EPB41L4B):​c.1753-2691C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,170 control chromosomes in the GnomAD database, including 2,544 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 0.17 (2544 hom., cov: 32)
• Consequence: EPB41L4B NM_019114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 2 publications found

Genes affected

EPB41L4B (HGNC:19818): (erythrocyte membrane protein band 4.1 like 4B) Predicted to be a structural constituent of cytoskeleton. Involved in several processes, including positive regulation of cell adhesion; positive regulation of keratinocyte migration; and wound healing. Acts upstream of or within actomyosin structure organization. Located in apical part of cell; cytosol; and plasma membrane. [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 (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4B	NM_019114.5	c.1753-2691C>T		intron_variant	Intron 17 of 25	ENST00000374566.8	NP_061987.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4B	ENST00000374566.8	c.1753-2691C>T		intron_variant	Intron 17 of 25	1	NM_019114.5	ENSP00000363694.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25527 AN: 152052 Hom.: 2544 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.168 AC: 25556 AN: 152170 Hom.: 2544 Cov.: 32 AF XY: 0.171 AC XY: 12753 AN XY: 74378

African (AFR) AF: 0.264 AC: 10952 AN: 41476

American (AMR) AF: 0.189 AC: 2890 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.113 AC: 583 AN: 5182

South Asian (SAS) AF: 0.136 AC: 655 AN: 4828

European-Finnish (FIN) AF: 0.207 AC: 2186 AN: 10582

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7752 AN: 68024

Other (OTH) AF: 0.148 AC: 313 AN: 2116

Alfa AF: 0.131 Hom.: 2323

Bravo AF: 0.175

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.24
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: rs7858370; hg19: chr9-111973020;