chr3-69204969-G-A

Variant names:

• chr3-69204969-G-A
• rs4075188
• NM_015123.3:c.877-6195C>T

Variant summary

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

The NM_015123.3(FRMD4B):​c.877-6195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 148,484 control chromosomes in the GnomAD database, including 576 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 0.089 (576 hom., cov: 30)
• Consequence: FRMD4B NM_015123.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.877-6195C>T		intron_variant	Intron 11 of 22	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.877-6195C>T		intron_variant	Intron 11 of 22	1	NM_015123.3	ENSP00000381549.3
FRMD4B	ENST00000470070.6	n.771-6195C>T		intron_variant	Intron 11 of 11	5
FRMD4B	ENST00000483668.5	n.489-6195C>T		intron_variant	Intron 6 of 6	4
FRMD4B	ENST00000487751.1	n.502-6195C>T		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13164 AN: 148380 Hom.: 575 Cov.: 30

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.0773

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.0765

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.0887 AC: 13176 AN: 148484 Hom.: 576 Cov.: 30 AF XY: 0.0862 AC XY: 6216 AN XY: 72094

African (AFR) AF: 0.0992 AC: 3956 AN: 39880

American (AMR) AF: 0.0745 AC: 1091 AN: 14652

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 265 AN: 3462

East Asian (EAS) AF: 0.0134 AC: 66 AN: 4940

South Asian (SAS) AF: 0.0317 AC: 150 AN: 4730

European-Finnish (FIN) AF: 0.0784 AC: 769 AN: 9810

Middle Eastern (MID) AF: 0.108 AC: 31 AN: 286

European-Non Finnish (NFE) AF: 0.0973 AC: 6591 AN: 67748

Other (OTH) AF: 0.0903 AC: 187 AN: 2070

Alfa AF: 0.0894 Hom.: 321

Bravo AF: 0.0880

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		1.6
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: rs4075188; hg19: chr3-69254120;