rs6913441

Variant names:

• chr6-168090591-C-T
• rs6913441
• ENST00000646385.1:c.-325+2380G>A

Variant summary

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

The ENST00000646385.1(FRMD1):​c.-325+2380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,092 control chromosomes in the GnomAD database, including 9,926 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 0.34 (9926 hom., cov: 34)
• Consequence: FRMD1 ENST00000646385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 3 publications found

Genes affected

FRMD1 (HGNC:21240): (FERM domain containing 1) Predicted to be involved in positive regulation of hippo signaling. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasmic side of apical plasma 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD1	XM_011536138.2	c.10+2380G>A		intron_variant	Intron 1 of 12		XP_011534440.1
FRMD1	XM_011536143.2	c.-38+2380G>A		intron_variant	Intron 1 of 11		XP_011534445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD1	ENST00000646385.1	c.-325+2380G>A		intron_variant	Intron 1 of 13			ENSP00000494166.1
FRMD1	ENST00000644440.1	c.-12+10834G>A		intron_variant	Intron 1 of 12			ENSP00000496464.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52029 AN: 151974 Hom.: 9915 Cov.: 34

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.342 AC: 52074 AN: 152092 Hom.: 9926 Cov.: 34 AF XY: 0.333 AC XY: 24771 AN XY: 74342

African (AFR) AF: 0.516 AC: 21390 AN: 41456

American (AMR) AF: 0.260 AC: 3976 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3468

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5174

South Asian (SAS) AF: 0.153 AC: 737 AN: 4830

European-Finnish (FIN) AF: 0.234 AC: 2474 AN: 10580

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21330 AN: 67988

Other (OTH) AF: 0.316 AC: 664 AN: 2104

Alfa AF: 0.314 Hom.: 4297

Bravo AF: 0.354

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs6913441; hg19: chr6-168491271;