5-38427214-G-T

Variant names:

• chr5-38427214-G-T
• rs140090894
• NM_152403.4:c.2016G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152403.4(EGFLAM):​c.2016G>T​(p.Glu672Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: EGFLAM NM_152403.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• Publications: 0 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-AS1 (HGNC:41169): (EGFLAM antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.10935229).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFLAM	NM_152403.4	MANE Select	c.2016G>T	p.Glu672Asp	missense	Exon 14 of 22	NP_689616.2
	EGFLAM	NM_001205301.2		c.2016G>T	p.Glu672Asp	missense	Exon 14 of 23	NP_001192230.1	Q63HQ2-1
	EGFLAM	NM_182798.3		c.1314G>T	p.Glu438Asp	missense	Exon 9 of 17	NP_877950.1	Q63HQ2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFLAM	ENST00000322350.10	TSL:1 MANE Select	c.2016G>T	p.Glu672Asp	missense	Exon 14 of 22	ENSP00000313084.5	Q63HQ2-2
	EGFLAM	ENST00000354891.7	TSL:1	c.2016G>T	p.Glu672Asp	missense	Exon 14 of 23	ENSP00000346964.3	Q63HQ2-1
	EGFLAM	ENST00000397202.6	TSL:1	c.114G>T	p.Glu38Asp	missense	Exon 4 of 12	ENSP00000380385.2	Q63HQ2-3

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000876 AC: 22 AN: 251134 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.0000289

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: 0.0000308 AC: 45 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20 AN XY: 727228

African (AFR) AF: 0.00122 AC: 41 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74478

African (AFR) AF: 0.00135 AC: 56 AN: 41576

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.000446

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.48		Loss of methylation at R674 (P = 0.1221)
MVP		0.71
MPC		0.46
ClinPred		0.36	T
GERP RS		2.5
Varity_R		0.68
gMVP		0.66
Mutation Taster		=82/18	polymorphism

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: rs140090894; hg19: chr5-38427316;