Variant 5-38370435-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152403.4(EGFLAM):c.685T>C(p.Trp229Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,613,854 control chromosomes in the GnomAD database, including 36,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5451 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30557 hom. )

Consequence

EGFLAM
NM_152403.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.303

Variant links:

Genes affected

EGFLAM (HGNC:26810): (EGF like, fibronectin type III and laminin G domains) Predicted to enable calcium ion binding activity and glycosaminoglycan binding activity. Predicted to be involved in animal organ morphogenesis and tissue development. Predicted to act upstream of or within extracellular matrix organization; peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan; and positive regulation of cell-substrate adhesion. Part of cell surface. [provided by Alliance of Genome Resources, Apr 2022]

EGFLAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.732277E-4).

BP6

Variant 5-38370435-T-C is Benign according to our data. Variant chr5-38370435-T-C is described in ClinVar as [Benign]. Clinvar id is 1235521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFLAM	NM_152403.4 link	c.685T>C	p.Trp229Arg	missense_variant	6/22	ENST00000322350.10	NP_689616.2	Q63HQ2-2
EGFLAM	NM_001205301.2 link	c.685T>C	p.Trp229Arg	missense_variant	6/23		NP_001192230.1	Q63HQ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10 link	c.685T>C	p.Trp229Arg	missense_variant	6/22	1	NM_152403.4	ENSP00000313084.5		Q63HQ2-2
EGFLAM	ENST00000354891.7 link	c.685T>C	p.Trp229Arg	missense_variant	6/23	1		ENSP00000346964.3		Q63HQ2-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38039

AN:

152050

Hom.:

5434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.203

AC:

50838

AN:

250688

Hom.:

5557

AF XY:

0.201

AC XY:

27305

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.200

AC:

292735

AN:

1461684

Hom.:

30557

Cov.:

AF XY:

0.200

AC XY:

145700

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.250

AC:

38096

AN:

152170

Hom.:

5451

Cov.:

AF XY:

0.249

AC XY:

18534

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.198

Hom.:

6221

Bravo

AF:

0.257

TwinsUK

AF:

0.197

AC:

730

ALSPAC

AF:

0.193

AC:

744

ESP6500AA

AF:

0.396

AC:

1746

ESP6500EA

AF:

0.193

AC:

1663

ExAC

AF:

0.210

AC:

25538

Asia WGS

AF:

0.201

AC:

696

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 09, 2019	This variant is associated with the following publications: (PMID: 28339009) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

DANN

Benign

0.68

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.29

T;T

MetaRNN

Benign

0.00027

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.93

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.028

Sift

Benign

0.66

T;T

Sift4G

Benign

0.84

T;T

Polyphen

0.0

B;B

Vest4

0.028

MutPred

0.35

Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);

MPC

0.16

ClinPred

0.000015

GERP RS

-2.0

Varity_R

0.082

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over