chr9-83530494-G-A

Position:

• chr9-83530494-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000304195.8(FRMD3):​c.147+7591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,078 control chromosomes in the GnomAD database, including 3,103 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 0.19 (3103 hom., cov: 32)
• Consequence: FRMD3 ENST00000304195.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+7591C>T		intron_variant		ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+7591C>T		intron_variant		1	NM_174938.6	ENSP00000303508	P1
FRMD3	ENST00000376438.5	c.147+7591C>T		intron_variant		2		ENSP00000365621

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28282 AN: 151960 Hom.: 3099 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.186 AC: 28306 AN: 152078 Hom.: 3103 Cov.: 32 AF XY: 0.186 AC XY: 13846 AN XY: 74342

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.198

Alfa AF: 0.157 Hom.: 325

Bravo AF: 0.189

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.9
DANN	Benign	0.78

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: rs11140139; hg19: chr9-86145409;