rs1324475

Variant names:

• chr9-120621631-C-T
• rs1324475
• NM_001080497.3:c.943+985G>A

Variant summary

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

The NM_001080497.3(MEGF9):​c.943+985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,002 control chromosomes in the GnomAD database, including 16,016 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 0.41 (16016 hom., cov: 31)
• Consequence: MEGF9 NM_001080497.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 10 publications found

Genes affected

MEGF9 (HGNC:3234): (multiple EGF like domains 9) Predicted to be involved in several processes, including animal organ morphogenesis; cell migration; and substrate adhesion-dependent cell spreading. Predicted to be integral component of membrane. Predicted to be active in basement membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF9	NM_001080497.3	c.943+985G>A		intron_variant	Intron 3 of 5	ENST00000373930.4	NP_001073966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF9	ENST00000373930.4	c.943+985G>A		intron_variant	Intron 3 of 5	2	NM_001080497.3	ENSP00000363040.3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62832 AN: 151884 Hom.: 15997 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.414 AC: 62854 AN: 152002 Hom.: 16016 Cov.: 31 AF XY: 0.428 AC XY: 31789 AN XY: 74290

African (AFR) AF: 0.106 AC: 4391 AN: 41484

American (AMR) AF: 0.560 AC: 8554 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1875 AN: 3470

East Asian (EAS) AF: 0.562 AC: 2899 AN: 5158

South Asian (SAS) AF: 0.679 AC: 3272 AN: 4822

European-Finnish (FIN) AF: 0.641 AC: 6748 AN: 10532

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33682 AN: 67944

Other (OTH) AF: 0.440 AC: 926 AN: 2106

Alfa AF: 0.451 Hom.: 23624

Bravo AF: 0.392

Asia WGS AF: 0.581 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.30
PhyloP100		-0.57
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: rs1324475; hg19: chr9-123383909;