11-65579415-C-G

Variant names:

• chr11-65579415-C-G
• rs189053067
• NM_001099409.3:c.237C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099409.3(EHBP1L1):​c.237C>G​(p.Asp79Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,563,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: EHBP1L1 NM_001099409.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.302
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051250964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099409.3. 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
	EHBP1L1	NM_001099409.3	MANE Select	c.237C>G	p.Asp79Glu	missense	Exon 3 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.237C>G	p.Asp79Glu	missense	Exon 3 of 18	NP_001338016.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1L1	ENST00000309295.9	TSL:1 MANE Select	c.237C>G	p.Asp79Glu	missense	Exon 3 of 19	ENSP00000312671.4	Q8N3D4
	EHBP1L1	ENST00000968317.1		c.237C>G	p.Asp79Glu	missense	Exon 3 of 20	ENSP00000638376.1
	EHBP1L1	ENST00000968331.1		c.237C>G	p.Asp79Glu	missense	Exon 3 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152118 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 29 AN: 180810 AF XY: 0.000176

Gnomad AFR exome AF: 0.0000898

Gnomad AMR exome AF: 0.000151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.000430

GnomAD4 exome AF: 0.000242 AC: 341 AN: 1411430 Hom.: 0 Cov.: 32 AF XY: 0.000218 AC XY: 152 AN XY: 697392

African (AFR) AF: 0.00 AC: 0 AN: 32472

American (AMR) AF: 0.000106 AC: 4 AN: 37790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24338

East Asian (EAS) AF: 0.00 AC: 0 AN: 38132

South Asian (SAS) AF: 0.00 AC: 0 AN: 78820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50148

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5648

European-Non Finnish (NFE) AF: 0.000298 AC: 324 AN: 1085536

Other (OTH) AF: 0.000171 AC: 10 AN: 58546

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152236 Hom.: 0 Cov.: 30 AF XY: 0.000202 AC XY: 15 AN XY: 74418

African (AFR) AF: 0.000120 AC: 5 AN: 41510

American (AMR) AF: 0.000196 AC: 3 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.000128

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000151 AC: 18

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	Pathogenic	0.74
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T
Eigen	Benign	0.082
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.30
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.70
MutPred		0.51		Gain of sheet (P = 0.0149)
MVP		0.70
MPC		0.25
ClinPred		0.25	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.26
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs189053067; hg19: chr11-65346886; COSMIC: COSV58574703; COSMIC: COSV58574703;