rs6787362

Positions:

• chr3-69178228-A-G

Variant summary

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

The NM_015123.3(FRMD4B):​c.2852-1572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,182 control chromosomes in the GnomAD database, including 746 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 0.093 (746 hom., cov: 32)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.2852-1572T>C		intron_variant		ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.2852-1572T>C		intron_variant		1	NM_015123.3	ENSP00000381549	P1
FRMD4B	ENST00000478263.5	c.1808-1572T>C		intron_variant		1		ENSP00000418682

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14086 AN: 152064 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0899

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.0925 AC: 14083 AN: 152182 Hom.: 746 Cov.: 32 AF XY: 0.0883 AC XY: 6571 AN XY: 74424

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.0898

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.122

Alfa AF: 0.100 Hom.: 866

Bravo AF: 0.0973

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.49

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: rs6787362; hg19: chr3-69227379;