chr14-51610371-T-C

Variant names:

• chr14-51610371-T-C
• rs1006973
• ENST00000356218.8:c.-147+39961T>C

Variant summary

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

The NM_001042481.3(FRMD6):​c.-147+39961T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 150,260 control chromosomes in the GnomAD database, including 35,015 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 0.67 (35015 hom., cov: 27)
• Consequence: FRMD6 NM_001042481.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 7 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]

FRMD6-AS2 (HGNC:43637): (FRMD6 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	NM_001042481.3		c.-147+39961T>C		intron	N/A	NP_001035946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD6	ENST00000356218.8	TSL:1	c.-147+39961T>C		intron	N/A	ENSP00000348550.4
	FRMD6	ENST00000554745.1	TSL:4	n.278-33081T>C		intron	N/A
	FRMD6	ENST00000556137.5	TSL:4	n.508+39961T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.667 AC: 100227 AN: 150174 Hom.: 35011 Cov.: 27

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.667 AC: 100250 AN: 150260 Hom.: 35015 Cov.: 27 AF XY: 0.670 AC XY: 49100 AN XY: 73240

African (AFR) AF: 0.444 AC: 18176 AN: 40914

American (AMR) AF: 0.739 AC: 11193 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2570 AN: 3462

East Asian (EAS) AF: 0.699 AC: 3594 AN: 5142

South Asian (SAS) AF: 0.746 AC: 3540 AN: 4746

European-Finnish (FIN) AF: 0.782 AC: 7698 AN: 9844

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.758 AC: 51356 AN: 67714

Other (OTH) AF: 0.663 AC: 1383 AN: 2086

Alfa AF: 0.732 Hom.: 135582

Bravo AF: 0.654

Asia WGS AF: 0.690 AC: 2396 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.40
DANN	Benign	0.44
PhyloP100		-1.2
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: rs1006973; hg19: chr14-52077089; COSMIC: COSV62288826;