rs12629229

Positions:

• chr3-69362071-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.162+23757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,118 control chromosomes in the GnomAD database, including 12,138 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 0.37 (12138 hom., cov: 33)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD4B	NM_015123.3	c.162+23757A>G		intron_variant		ENST00000398540.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD4B	ENST00000398540.8	c.162+23757A>G		intron_variant		1	NM_015123.3	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55564 AN: 152000 Hom.: 12104 Cov.: 33

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.366 AC: 55661 AN: 152118 Hom.: 12138 Cov.: 33 AF XY: 0.361 AC XY: 26878 AN XY: 74386

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.356

Alfa AF: 0.325 Hom.: 1520

Bravo AF: 0.380

Asia WGS AF: 0.368 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.73

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: rs12629229; hg19: chr3-69411222;