rs12629229

Variant names:

• chr3-69362071-T-C
• rs12629229
• NM_015123.3:c.162+23757A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.162+23757A>G		intron_variant	Intron 1 of 22	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.162+23757A>G		intron_variant	Intron 1 of 22	1	NM_015123.3	ENSP00000381549.3

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

African (AFR) AF: 0.613 AC: 25441 AN: 41476

American (AMR) AF: 0.325 AC: 4971 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1782 AN: 5174

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4812

European-Finnish (FIN) AF: 0.259 AC: 2742 AN: 10582

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17354 AN: 67998

Other (OTH) AF: 0.356 AC: 751 AN: 2112

Alfa AF: 0.334 Hom.: 1674

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
PhyloP100		-0.82
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: rs12629229; hg19: chr3-69411222;