ENST00000646385.1:c.-325+3083C>T

Variant names:

• chr6-168089888-G-A
• rs9364220
• ENST00000646385.1:c.-325+3083C>T

Variant summary

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

The ENST00000646385.1(FRMD1):​c.-325+3083C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,064 control chromosomes in the GnomAD database, including 7,975 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 0.31 (7975 hom., cov: 33)
• Consequence: FRMD1 ENST00000646385.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 10 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD1	XM_011536138.2	c.10+3083C>T		intron_variant	Intron 1 of 12		XP_011534440.1
FRMD1	XM_011536143.2	c.-38+3083C>T		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+3083C>T		intron_variant	Intron 1 of 13			ENSP00000494166.1
FRMD1	ENST00000644440.1	c.-11-10864C>T		intron_variant	Intron 1 of 12			ENSP00000496464.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46931 AN: 151946 Hom.: 7978 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.309 AC: 46942 AN: 152064 Hom.: 7975 Cov.: 33 AF XY: 0.316 AC XY: 23520 AN XY: 74334

African (AFR) AF: 0.169 AC: 7030 AN: 41528

American (AMR) AF: 0.361 AC: 5522 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2758 AN: 5152

South Asian (SAS) AF: 0.537 AC: 2582 AN: 4810

European-Finnish (FIN) AF: 0.352 AC: 3724 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22629 AN: 67930

Other (OTH) AF: 0.342 AC: 722 AN: 2110

Alfa AF: 0.327 Hom.: 29613

Bravo AF: 0.298

Asia WGS AF: 0.525 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs9364220; hg19: chr6-168490568; COSMIC: COSV60303283;