rs6776243

Positions:

• chr3-69204505-T-C

Variant summary

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

The NM_015123.3(FRMD4B):​c.877-5731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 152,282 control chromosomes in the GnomAD database, including 633 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 0.090 (633 hom., cov: 32)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3	c.877-5731A>G		intron_variant		ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8	c.877-5731A>G		intron_variant		1	NM_015123.3	P1
FRMD4B	ENST00000470070.6	n.771-5731A>G		intron_variant, non_coding_transcript_variant		5
FRMD4B	ENST00000483668.5	n.489-5731A>G		intron_variant, non_coding_transcript_variant		4
FRMD4B	ENST00000487751.1	n.502-5731A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13672 AN: 152164 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.0899 AC: 13685 AN: 152282 Hom.: 633 Cov.: 32 AF XY: 0.0871 AC XY: 6489 AN XY: 74492

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0747

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0928 Hom.: 69

Bravo AF: 0.0911

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
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: rs6776243; hg19: chr3-69253656;