5-38350602-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_152403.4(EGFLAM):c.393C>G(p.Val131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,998 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (5 hom.)
• Consequence: EGFLAM NM_152403.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.634

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-38350602-C-G is Benign according to our data. Variant chr5-38350602-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFLAM	NM_152403.4	c.393C>G	p.Val131=	synonymous_variant	4/22	ENST00000322350.10
EGFLAM	NM_001205301.2	c.393C>G	p.Val131=	synonymous_variant	4/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFLAM	ENST00000322350.10	c.393C>G	p.Val131=	synonymous_variant	4/22	1	NM_152403.4	P3
EGFLAM	ENST00000354891.7	c.393C>G	p.Val131=	synonymous_variant	4/23	1		A2
EGFLAM	ENST00000504709.1	c.*435C>G		3_prime_UTR_variant, NMD_transcript_variant	5/6	3

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 252 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00175 AC: 439 AN: 250960 Hom.: 1 AF XY: 0.00194 AC XY: 263 AN XY: 135606

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00200

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.00236

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.00168 AC: 2457 AN: 1461664 Hom.: 5 Cov.: 31 AF XY: 0.00177 AC XY: 1289 AN XY: 727126

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00197

Gnomad4 FIN exome AF: 0.00329

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00165 AC: 252 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.00170 AC XY: 127 AN XY: 74492

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00217 Hom.: 0

Bravo AF: 0.00136

EpiCase AF: 0.00185

EpiControl AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

EGFLAM: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.7
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs148290116; hg19: chr5-38350704;