3-69458148-G-C

Variant names:

• chr3-69458148-G-C
• rs7631421
• ENST00000459638.5:c.-128-25387C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000497880.5(FRMD4B):​c.-128-25387C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,090 control chromosomes in the GnomAD database, including 9,980 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 0.35 (9980 hom., cov: 32)
• Consequence: FRMD4B ENST00000497880.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000497880.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD4B	ENST00000459638.5	TSL:5	c.-128-25387C>G		intron	N/A	ENSP00000417550.1	C9JA15
	FRMD4B	ENST00000497880.5	TSL:4	c.-128-25387C>G		intron	N/A	ENSP00000417765.1	C9J7M5

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53760 AN: 151972 Hom.: 9972 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.354 AC: 53787 AN: 152090 Hom.: 9980 Cov.: 32 AF XY: 0.351 AC XY: 26088 AN XY: 74328

African (AFR) AF: 0.462 AC: 19150 AN: 41486

American (AMR) AF: 0.315 AC: 4816 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1558 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1625 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3098 AN: 10562

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21653 AN: 67988

Other (OTH) AF: 0.345 AC: 728 AN: 2112

Alfa AF: 0.169 Hom.: 287

Bravo AF: 0.359

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		0.042

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7631421;

hg19: chr3-69507299;