dbSNP rs919291: EGFLAM:c.97+31249G>A (chr5-38290100-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

1 publications found

Variant links:

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 links:

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

EGFLAM-AS4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
EGFLAM	NM_152403.4 link	c.97+31249G>A	intron_variant	Intron 1 of 21	ENST00000322350.10	NP_689616.2
EGFLAM	NM_001205301.2 link	c.97+31249G>A	intron_variant	Intron 1 of 22		NP_001192230.1
EGFLAM-AS4	NR_046219.1 link	n.387+500C>T	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EGFLAM	ENST00000322350.10 link	c.97+31249G>A	intron_variant	Intron 1 of 21	1	NM_152403.4	ENSP00000313084.5
EGFLAM	ENST00000354891.7 link	c.97+31249G>A	intron_variant	Intron 1 of 22	1		ENSP00000346964.3
EGFLAM-AS4	ENST00000512496.1 link	n.387+500C>T	intron_variant	Intron 1 of 3	1
EGFLAM	ENST00000504709.1 link	n.98-15332G>A	intron_variant	Intron 1 of 5	3		ENSP00000426437.1

Frequencies

GnomAD3 genomes

AF:

0.00728

AC:

1107

AN:

152164

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00745

AC XY:

555

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41562

American (AMR)

AF:

0.0102

AC:

156

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0456

AC:

236

AN:

5170

South Asian (SAS)

AF:

0.0339

AC:

163

AN:

4814

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00648

AC:

441

AN:

68022

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00678

Hom.:

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

(source)

DANN

Benign

0.49

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over