rs6591182

Positions:

• chr11-65582285-T-C
• chr11-65582285-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099409.3(EHBP1L1):​c.1613T>C​(p.Val538Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V538G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EHBP1L1 NM_001099409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

Genes affected

EHBP1L1 (HGNC:30682): (EH domain binding protein 1 like 1) Predicted to be involved in actin cytoskeleton organization. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13946444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EHBP1L1	NM_001099409.3	c.1613T>C	p.Val538Ala	missense_variant	9/19	ENST00000309295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHBP1L1	ENST00000309295.9	c.1613T>C	p.Val538Ala	missense_variant	9/19	1	NM_001099409.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 86

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.075
Eigen_PC	Benign	0.017
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.36	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.99	P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.34	T
Polyphen		0.49	P
Vest4		0.30
MutPred		0.14		Gain of glycosylation at P536 (P = 0.1087);
MVP		0.82
MPC		0.14
ClinPred		0.33	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs6591182; hg19: chr11-65349756;