rs6913441

Positions:

• chr6-168090591-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FRMD1	XM_011536138.2	c.10+2380G>A		intron_variant			XP_011534440.1
FRMD1	XM_011536143.2	c.-38+2380G>A		intron_variant			XP_011534445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD1	ENST00000644440.1	c.-12+10834G>A		intron_variant				ENSP00000496464	A2
FRMD1	ENST00000646385.1	c.-325+2380G>A		intron_variant				ENSP00000494166	P2

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

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.316

Alfa AF: 0.313 Hom.: 3810

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6913441; hg19: chr6-168491271;