NM_001267046.2:c.-147+3763C>T

Variant names:

• chr14-51655759-C-T
• rs17666653
• NM_001267046.2:c.-147+3763C>T

Variant summary

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

The NM_001267046.2(FRMD6):​c.-147+3763C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,042 control chromosomes in the GnomAD database, including 4,528 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 0.24 (4528 hom., cov: 32)
• Consequence: FRMD6 NM_001267046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 5 publications found

Genes affected

FRMD6 (HGNC:19839): (FERM domain containing 6) Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within apical constriction; cellular protein localization; and regulation of actin filament-based process. Predicted to be located in apical junction complex. Predicted to be active in cytoskeleton. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD6	NM_001267046.2	c.-147+3763C>T		intron_variant	Intron 1 of 13	ENST00000344768.10	NP_001253975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD6	ENST00000344768.10	c.-147+3763C>T		intron_variant	Intron 1 of 13	2	NM_001267046.2	ENSP00000343899.6

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36210 AN: 151924 Hom.: 4523 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.238 AC: 36245 AN: 152042 Hom.: 4528 Cov.: 32 AF XY: 0.238 AC XY: 17654 AN XY: 74330

African (AFR) AF: 0.327 AC: 13563 AN: 41460

American (AMR) AF: 0.236 AC: 3612 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3468

East Asian (EAS) AF: 0.0904 AC: 468 AN: 5178

South Asian (SAS) AF: 0.231 AC: 1111 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 2004 AN: 10576

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14098 AN: 67944

Other (OTH) AF: 0.239 AC: 505 AN: 2116

Alfa AF: 0.219 Hom.: 6366

Bravo AF: 0.246

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		0.015
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: rs17666653; hg19: chr14-52122477;