rs1888747

Variant names:

• chr9-83540636-C-G
• rs1888747
• XM_017014588.2:c.24+19534G>C

Variant summary

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

The XM_017014588.2(FRMD3):​c.24+19534G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,054 control chromosomes in the GnomAD database, including 46,421 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 0.78 (46421 hom., cov: 31)
• Consequence: FRMD3 XM_017014588.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 29 publications found

Genes affected

FRMD3 (HGNC:24125): (FERM domain containing 3) The protein encoded by this gene is a single pass membrane protein primarily found in ovaries. A similar protein in erythrocytes helps determine the shape of red blood cells, but the function of the encoded protein has not been determined. There is some evidence that this is a tumor suppressor gene, and there is also evidence linking defects in this gene to susceptibility to diabetic nephropathy in type 1 diabetes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	XM_017014588.2	c.24+19534G>C		intron_variant	Intron 1 of 13		XP_016870077.1
FRMD3	XM_024447487.2	c.-142+34274G>C		intron_variant	Intron 2 of 14		XP_024303255.1
FRMD3	XM_047423155.1	c.-142+44917G>C		intron_variant	Intron 1 of 13		XP_047279111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117791 AN: 151936 Hom.: 46349 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.776 AC: 117924 AN: 152054 Hom.: 46421 Cov.: 31 AF XY: 0.776 AC XY: 57660 AN XY: 74308

African (AFR) AF: 0.928 AC: 38532 AN: 41510

American (AMR) AF: 0.739 AC: 11285 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3464

East Asian (EAS) AF: 0.741 AC: 3830 AN: 5172

South Asian (SAS) AF: 0.806 AC: 3872 AN: 4804

European-Finnish (FIN) AF: 0.736 AC: 7764 AN: 10552

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47984 AN: 67970

Other (OTH) AF: 0.743 AC: 1567 AN: 2108

Alfa AF: 0.755 Hom.: 5431

Bravo AF: 0.777

Asia WGS AF: 0.790 AC: 2750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.76
PhyloP100		-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1888747; hg19: chr9-86155551;