rs2378658

chr9-83289863-A-Gchr9-83289863-A-T

Variant summary

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

The NM_174938.6(FRMD3):c.1195+740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,148 control chromosomes in the GnomAD database, including 24,421 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 0.55 (24421 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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]

LOC124902190 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.1195+740T>C		intron_variant		ENST00000304195.8
LOC124902190	XR_007061614.1	n.5563A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.1195+740T>C		intron_variant		1	NM_174938.6	P1
FRMD3	ENST00000376434.5	c.613+740T>C		intron_variant		1
FRMD3	ENST00000621208.4	c.1063+740T>C		intron_variant		1
FRMD3	ENST00000376438.5	c.1195+740T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83344 AN: 152030 Hom.: 24405 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.548 AC: 83385 AN: 152148 Hom.: 24421 Cov.: 33 AF XY: 0.555 AC XY: 41285 AN XY: 74372

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.618

Gnomad4 OTH AF: 0.585

Alfa AF: 0.612 Hom.: 59323

Bravo AF: 0.527

Asia WGS AF: 0.756 AC: 2622 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.15
Dann	Benign	0.63

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: rs2378658; hg19: chr9-85904778;