dbSNP rs755233039: EMB:p.Ile76Phe (chr5-50411354-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_198449.3(EMB):c.226A>T(p.Ile76Phe) 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. 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. I76V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMB
NM_198449.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.872

Publications

0 publications found

Variant links:

Genes affected

EMB (HGNC:30465): (embigin) This gene encodes a transmembrane glycoprotein that is a member of the immunoglobulin superfamily. The encoded protein may be involved in cell growth and development by mediating interactions between the cell and extracellular matrix. A pseudogene of this gene is found on chromosome 1. [provided by RefSeq, Jan 2009]

EMB links:

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ACMG classification

Classification was made for transcript

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=0.30987722).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198449.3. 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
	EMB	NM_198449.3	MANE Select	c.226A>T	p.Ile76Phe	missense	Exon 3 of 9	NP_940851.1	Q6PCB8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMB	ENST00000303221.10	TSL:1 MANE Select	c.226A>T	p.Ile76Phe	missense	Exon 3 of 9	ENSP00000302289.5	Q6PCB8-1
EMB	ENST00000872546.1		c.142A>T	p.Ile48Phe	missense	Exon 2 of 8	ENSP00000542605.1
EMB	ENST00000514111.1	TSL:2	c.76A>T	p.Ile26Phe	missense	Exon 3 of 9	ENSP00000426404.1	Q6PCB8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246938

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.88e-7

AC:

AN:

1454300

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33276

American (AMR)

AF:

0.0000228

AC:

AN:

43892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39474

South Asian (SAS)

AF:

0.00

AC:

AN:

84802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107976

Other (OTH)

AF:

0.00

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.78

M_CAP

Benign

0.016

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.87

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.10

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.54

MutPred

0.43

Gain of disorder (P = 0.147)

MVP

0.36

MPC

0.61

ClinPred

0.71

GERP RS

1.2

Varity_R

0.17

gMVP

0.83

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over