rs3751464

Positions:

• chr14-51651174-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356218.8(FRMD6):​c.-146-38517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,348 control chromosomes in the GnomAD database, including 44,003 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 0.76 (43933 hom., cov: 32)
  • Exomes 𝑓: 0.81 (70 hom.)
• Consequence: FRMD6 ENST00000356218.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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-AS1 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD6-AS1	NR_037676.1	n.571A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD6	ENST00000356218.8	c.-146-38517T>C		intron_variant		1		P1
FRMD6-AS2	ENST00000617151.1	n.571A>G		non_coding_transcript_exon_variant	1/1
FRMD6	ENST00000556137.5	n.509-38517T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115038 AN: 152014 Hom.: 43885 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.772

GnomAD4 exome AF: 0.810 AC: 175 AN: 216 Hom.: 70 Cov.: 0 AF XY: 0.792 AC XY: 133 AN XY: 168

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.875

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.757 AC: 115146 AN: 152132 Hom.: 43933 Cov.: 32 AF XY: 0.753 AC XY: 56004 AN XY: 74376

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.775

Alfa AF: 0.793 Hom.: 59634

Bravo AF: 0.757

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.4
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751464; hg19: chr14-52117892;