11-65579348-G-A

Variant names:

• chr11-65579348-G-A
• rs1857478473
• NM_001099409.3:c.170G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099409.3(EHBP1L1):​c.170G>A​(p.Ser57Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,406,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S57I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EHBP1L1 NM_001099409.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39898518).

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.170G>A	p.Ser57Asn	missense	Exon 3 of 19	NP_001092879.1	Q8N3D4
	EHBP1L1	NM_001351087.2		c.170G>A	p.Ser57Asn	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.170G>A	p.Ser57Asn	missense	Exon 3 of 19	ENSP00000312671.4	Q8N3D4
	EHBP1L1	ENST00000968317.1		c.170G>A	p.Ser57Asn	missense	Exon 3 of 20	ENSP00000638376.1
	EHBP1L1	ENST00000968331.1		c.170G>A	p.Ser57Asn	missense	Exon 3 of 18	ENSP00000638390.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1406976 Hom.: 0 Cov.: 32 AF XY: 0.00000288 AC XY: 2 AN XY: 694516

African (AFR) AF: 0.00 AC: 0 AN: 32544

American (AMR) AF: 0.00 AC: 0 AN: 37466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24136

East Asian (EAS) AF: 0.00 AC: 0 AN: 37830

South Asian (SAS) AF: 0.0000256 AC: 2 AN: 78232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083086

Other (OTH) AF: 0.00 AC: 0 AN: 58354

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.74
MPC		0.26
ClinPred		0.94	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.20
Mutation Taster		=85/15	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: rs1857478473; hg19: chr11-65346819;