11-65579109-C-A

Variant names:

• chr11-65579109-C-A
• rs772602480
• NM_001099409.3:c.136C>A

Variant summary

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

The NM_001099409.3(EHBP1L1):​c.136C>A​(p.Arg46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R46C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EHBP1L1 NM_001099409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1L1	NM_001099409.3	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 19	ENST00000309295.9	NP_001092879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1L1	ENST00000309295.9	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 19	1	NM_001099409.3	ENSP00000312671.4
EHBP1L1	ENST00000533237.5	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 12	5		ENSP00000431996.1
EHBP1L1	ENST00000634639.1	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 12	5		ENSP00000489002.1
EHBP1L1	ENST00000531106.1	n.110C>A		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442522 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715568

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: 0.00

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000882 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.69	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.6	D;D;.
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.83
MutPred		0.54		Loss of MoRF binding (P = 0.1108);Loss of MoRF binding (P = 0.1108);Loss of MoRF binding (P = 0.1108);
MVP		0.83
MPC		0.21
ClinPred		1.0	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.80
gMVP		0.80

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: rs772602480; hg19: chr11-65346580;