chr11-65579128-G-T

Position:

• chr11-65579128-G-T

Variant summary

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

The NM_001099409.3(EHBP1L1):​c.155G>T​(p.Cys52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EHBP1L1 NM_001099409.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

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]

EHBP1L1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1L1	NM_001099409.3	c.155G>T	p.Cys52Phe	missense_variant	2/19	ENST00000309295.9	NP_001092879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1L1	ENST00000309295.9	c.155G>T	p.Cys52Phe	missense_variant	2/19	1	NM_001099409.3	ENSP00000312671.4
EHBP1L1	ENST00000533237.5	c.155G>T	p.Cys52Phe	missense_variant	2/12	5		ENSP00000431996.1
EHBP1L1	ENST00000634639.1	c.155G>T	p.Cys52Phe	missense_variant	2/12	5		ENSP00000489002.1
EHBP1L1	ENST00000531106.1	n.129G>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441654 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 715034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.155G>T (p.C52F) alteration is located in exon 2 (coding exon 2) of the EHBP1L1 gene. This alteration results from a G to T substitution at nucleotide position 155, causing the cysteine (C) at amino acid position 52 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-7.0	D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;D;.
Sift4G	Uncertain	0.0060	D;D;T
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.26		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.71
MPC		0.30
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.75
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65346599;