rs11140116

Variant names:

• chr9-83487553-C-T
• rs11140116
• NM_174938.6:c.147+50532G>A

Variant summary

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

The NM_174938.6(FRMD3):​c.147+50532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 152,198 control chromosomes in the GnomAD database, including 677 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 0.082 (677 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+50532G>A		intron_variant	Intron 1 of 13	ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+50532G>A		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+50532G>A		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12436 AN: 152080 Hom.: 676 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0497

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0846

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

GnomAD4 genome AF: 0.0819 AC: 12465 AN: 152198 Hom.: 677 Cov.: 33 AF XY: 0.0798 AC XY: 5939 AN XY: 74408

African (AFR) AF: 0.147 AC: 6109 AN: 41510

American (AMR) AF: 0.0586 AC: 895 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3468

East Asian (EAS) AF: 0.169 AC: 876 AN: 5178

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4826

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10592

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0521 AC: 3541 AN: 68018

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0587 Hom.: 224

Bravo AF: 0.0896

Asia WGS AF: 0.104 AC: 362 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.62
PhyloP100		0.29
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: rs11140116; hg19: chr9-86102468; COSMIC: COSV58458098;