chr9-109192339-C-T

Variant names:

• chr9-109192339-C-T
• rs200634407
• NM_019114.5:c.2240G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_019114.5(EPB41L4B):​c.2240G>A​(p.Gly747Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,611,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: EPB41L4B NM_019114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28052473).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019114.5. 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
	EPB41L4B	NM_019114.5	MANE Select	c.2240G>A	p.Gly747Glu	missense	Exon 22 of 26	NP_061987.3
	EPB41L4B	NM_001385623.1		c.2249G>A	p.Gly750Glu	missense	Exon 22 of 25	NP_001372552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4B	ENST00000374566.8	TSL:1 MANE Select	c.2240G>A	p.Gly747Glu	missense	Exon 22 of 26	ENSP00000363694.3	Q9H329-1
	EPB41L4B	ENST00000952218.1		c.2240G>A	p.Gly747Glu	missense	Exon 22 of 27	ENSP00000622277.1
	EPB41L4B	ENST00000952215.1		c.2249G>A	p.Gly750Glu	missense	Exon 22 of 26	ENSP00000622274.1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000384 AC: 95 AN: 247710 AF XY: 0.000387

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000604

Gnomad NFE exome AF: 0.000604

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000412 AC: 601 AN: 1459792 Hom.: 0 Cov.: 30 AF XY: 0.000397 AC XY: 288 AN XY: 726106

African (AFR) AF: 0.0000899 AC: 3 AN: 33378

American (AMR) AF: 0.0000451 AC: 2 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85930

European-Finnish (FIN) AF: 0.000524 AC: 28 AN: 53394

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.000489 AC: 543 AN: 1111016

Other (OTH) AF: 0.000249 AC: 15 AN: 60276

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74354

African (AFR) AF: 0.0000965 AC: 4 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000445 Hom.: 0

Bravo AF: 0.000230

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000800 AC: 3

ESP6500EA AF: 0.000609 AC: 5

ExAC AF: 0.000414 AC: 50

EpiCase AF: 0.000546

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	0.97	L
PhyloP100		4.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.21	T
Polyphen		0.95	P
Vest4		0.53
MVP		0.27
MPC		0.79
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.23
gMVP		0.19
Mutation Taster		=79/21	polymorphism

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: rs200634407; hg19: chr9-111954619; COSMIC: COSV63124053; COSMIC: COSV63124053;