rs10512683

Variant names:

• chr5-38397998-T-C
• rs10512683
• NM_152403.4:c.713-8128T>C

Variant summary

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

The NM_152403.4(EGFLAM):​c.713-8128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 152,250 control chromosomes in the GnomAD database, including 230 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 0.031 (230 hom., cov: 32)
• Consequence: EGFLAM NM_152403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFLAM	NM_152403.4	c.713-8128T>C		intron_variant	Intron 6 of 21	ENST00000322350.10	NP_689616.2
EGFLAM	NM_001205301.2	c.713-8128T>C		intron_variant	Intron 6 of 22		NP_001192230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10	c.713-8128T>C		intron_variant	Intron 6 of 21	1	NM_152403.4	ENSP00000313084.5
EGFLAM	ENST00000354891.7	c.713-8128T>C		intron_variant	Intron 6 of 22	1		ENSP00000346964.3

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4720 AN: 152130 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00974

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00573

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0310 AC: 4722 AN: 152250 Hom.: 230 Cov.: 32 AF XY: 0.0299 AC XY: 2225 AN XY: 74448

African (AFR) AF: 0.0971 AC: 4031 AN: 41530

American (AMR) AF: 0.0110 AC: 168 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4822

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00573 AC: 390 AN: 68022

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0194 Hom.: 39

Bravo AF: 0.0350

Asia WGS AF: 0.00635 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.21
PhyloP100		-0.94
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: rs10512683; hg19: chr5-38398100;