5-38440499-A-G

Variant names:

• chr5-38440499-A-G
• rs2956597
• NM_152403.4:c.2464+2044A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152403.4(EGFLAM):​c.2464+2044A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,020 control chromosomes in the GnomAD database, including 11,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (11039 hom., cov: 32)
• Consequence: EGFLAM NM_152403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 1 publications found

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-AS5 (HGNC:58126):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFLAM	NM_152403.4	MANE Select	c.2464+2044A>G		intron	N/A	NP_689616.2
	EGFLAM	NM_001205301.2		c.2464+2044A>G		intron	N/A	NP_001192230.1
	EGFLAM	NM_182798.3		c.1762+2044A>G		intron	N/A	NP_877950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFLAM	ENST00000322350.10	TSL:1 MANE Select	c.2464+2044A>G		intron	N/A	ENSP00000313084.5
	EGFLAM	ENST00000354891.7	TSL:1	c.2464+2044A>G		intron	N/A	ENSP00000346964.3
	EGFLAM	ENST00000397202.6	TSL:1	c.562+2044A>G		intron	N/A	ENSP00000380385.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45124 AN: 151902 Hom.: 11002 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45215 AN: 152020 Hom.: 11039 Cov.: 32 AF XY: 0.289 AC XY: 21462 AN XY: 74314

African (AFR) AF: 0.676 AC: 28001 AN: 41414

American (AMR) AF: 0.205 AC: 3130 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3466

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5176

South Asian (SAS) AF: 0.0841 AC: 406 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1534 AN: 10566

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10420 AN: 67986

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.189 Hom.: 6866

Bravo AF: 0.320

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.49
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2956597; hg19: chr5-38440601;