rs12654591

Variant names:

• chr5-38271480-C-A
• rs12654591
• NM_152403.4:c.97+12629C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-38271480-C-A
• chr5-38271480-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152403.4(EGFLAM):​c.97+12629C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 152,226 control chromosomes in the GnomAD database, including 47 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 0.017 (47 hom., cov: 33)
• Consequence: EGFLAM NM_152403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 2 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=-0.72).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0175 (2660/152226) while in subpopulation EAS AF = 0.0456 (236/5170). AF 95% confidence interval is 0.0409. There are 47 homozygotes in GnomAd4. There are 1331 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFLAM	NM_152403.4	c.97+12629C>A		intron_variant	Intron 1 of 21	ENST00000322350.10	NP_689616.2
EGFLAM	NM_001205301.2	c.97+12629C>A		intron_variant	Intron 1 of 22		NP_001192230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10	c.97+12629C>A		intron_variant	Intron 1 of 21	1	NM_152403.4	ENSP00000313084.5
EGFLAM	ENST00000354891.7	c.97+12629C>A		intron_variant	Intron 1 of 22	1		ENSP00000346964.3
EGFLAM	ENST00000504709.1	n.97+12629C>A		intron_variant	Intron 1 of 5	3		ENSP00000426437.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2660 AN: 152108 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0175 AC: 2660 AN: 152226 Hom.: 47 Cov.: 33 AF XY: 0.0179 AC XY: 1331 AN XY: 74428

African (AFR) AF: 0.0326 AC: 1355 AN: 41526

American (AMR) AF: 0.0128 AC: 196 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5170

South Asian (SAS) AF: 0.0349 AC: 168 AN: 4820

European-Finnish (FIN) AF: 0.0186 AC: 197 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00703 AC: 478 AN: 68014

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.0104 Hom.: 30

Bravo AF: 0.0170

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		0.019
Mutation Taster		=100/0	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: rs12654591; hg19: chr5-38271582;