Genetic Variant NM_032048.3:c.47C>T (chr18-2847235-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032048.3(EMILIN2):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 1,116,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A16E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

EMILIN2
NM_032048.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.642

Publications

0 publications found

Variant links:

Genes affected

EMILIN2 (HGNC:19881): (elastin microfibril interfacer 2) Predicted to enable extracellular matrix constituent conferring elasticity. Predicted to be involved in cell adhesion. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EMILIN2 links:

ENSG00000289061 (HGNC:):

ENSG00000289061 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06687021).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032048.3. 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
	EMILIN2	NM_032048.3	MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 8	NP_114437.2	Q9BXX0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMILIN2	ENST00000254528.4	TSL:1 MANE Select	c.47C>T	p.Ala16Val	missense	Exon 1 of 8	ENSP00000254528.3	Q9BXX0
EMILIN2	ENST00000942047.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 7	ENSP00000612106.1
EMILIN2	ENST00000942046.1		c.47C>T	p.Ala16Val	missense	Exon 1 of 7	ENSP00000612105.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

8354

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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

AF:

0.00000179

AC:

AN:

1116288

Hom.:

Cov.:

AF XY:

0.00000372

AC XY:

AN XY:

537932

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22520

American (AMR)

AF:

0.00

AC:

AN:

9640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14500

East Asian (EAS)

AF:

0.00

AC:

AN:

25270

South Asian (SAS)

AF:

0.00

AC:

AN:

33578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2950

European-Non Finnish (NFE)

AF:

0.00000213

AC:

AN:

940604

Other (OTH)

AF:

0.00

AC:

AN:

44032

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0090

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.53

M_CAP

Benign

0.046

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.64

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.51

REVEL

Benign

0.022

Sift

Benign

0.48

Sift4G

Benign

0.49

Polyphen

0.0050

Vest4

0.23

MutPred

0.29

Gain of loop (P = 0.0079)

MVP

0.12

MPC

0.084

ClinPred

0.12

GERP RS

1.6

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.051

gMVP

0.36

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

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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