rs12654591

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFLAM	NM_152403.4	c.97+12629C>A		intron_variant		ENST00000322350.10
EGFLAM	NM_001205301.2	c.97+12629C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFLAM	ENST00000322350.10	c.97+12629C>A		intron_variant		1	NM_152403.4	P3
EGFLAM	ENST00000354891.7	c.97+12629C>A		intron_variant		1		A2
EGFLAM	ENST00000504709.1	c.97+12629C>A		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.00703

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00820 Hom.: 11

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12654591; hg19: chr5-38271582;