rs919291

Positions:

• chr5-38290100-G-A

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+31249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00726 in 152,282 control chromosomes in the GnomAD database, including 18 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 0.0073 (18 hom., cov: 32)
• Consequence: EGFLAM NM_152403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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-AS4 (HGNC:41166): (EGFLAM antisense RNA 4)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00726 (1105/152282) while in subpopulation EAS AF= 0.0456 (236/5170). AF 95% confidence interval is 0.0409. There are 18 homozygotes in gnomad4. There are 555 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFLAM	NM_152403.4	c.97+31249G>A		intron_variant		ENST00000322350.10	NP_689616.2
EGFLAM-AS4	NR_046219.1	n.387+500C>T		intron_variant, non_coding_transcript_variant
EGFLAM	NM_001205301.2	c.97+31249G>A		intron_variant			NP_001192230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFLAM	ENST00000322350.10	c.97+31249G>A		intron_variant		1	NM_152403.4	ENSP00000313084	P3
EGFLAM	ENST00000354891.7	c.97+31249G>A		intron_variant		1		ENSP00000346964	A2
EGFLAM-AS4	ENST00000512496.1	n.387+500C>T		intron_variant, non_coding_transcript_variant		1
EGFLAM	ENST00000504709.1	c.98-15332G>A		intron_variant, NMD_transcript_variant		3		ENSP00000426437

Frequencies

GnomAD3 genomes AF: 0.00728 AC: 1107 AN: 152164 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00648

Gnomad OTH AF: 0.00765

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

GnomAD4 genome AF: 0.00726 AC: 1105 AN: 152282 Hom.: 18 Cov.: 32 AF XY: 0.00745 AC XY: 555 AN XY: 74460

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0339

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00648

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00678 Hom.: 0

Bravo AF: 0.00746

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.49

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: rs919291; hg19: chr5-38290202;