rs9831516

Variant names:

• chr3-69180910-G-A
• rs9831516
• NM_015123.3:c.2840C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-69180910-G-A
• chr3-69180910-G-C

Variant summary

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

The NM_015123.3(FRMD4B):​c.2840C>T​(p.Ser947Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.951 in 1,602,998 control chromosomes in the GnomAD database, including 733,282 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 0.87 (59136 hom., cov: 31)
  • Exomes 𝑓: 0.96 (674146 hom.)
• Consequence: FRMD4B NM_015123.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 33 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 (MetaRNN=8.4222E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.2840C>T	p.Ser947Leu	missense_variant	Exon 21 of 23	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.2840C>T	p.Ser947Leu	missense_variant	Exon 21 of 23	1	NM_015123.3	ENSP00000381549.3
FRMD4B	ENST00000478263.5	c.1796C>T	p.Ser599Leu	missense_variant	Exon 11 of 13	1		ENSP00000418682.1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131849 AN: 152000 Hom.: 59129 Cov.: 31

Gnomad AFR AF: 0.644

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.896

GnomAD2 exomes AF: 0.904 AC: 221823 AN: 245344 AF XY: 0.909

Gnomad AFR exome AF: 0.642

Gnomad AMR exome AF: 0.888

Gnomad ASJ exome AF: 0.991

Gnomad EAS exome AF: 0.594

Gnomad FIN exome AF: 0.992

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.949

GnomAD4 exome AF: 0.960 AC: 1392429 AN: 1450880 Hom.: 674146 Cov.: 32 AF XY: 0.957 AC XY: 689619 AN XY: 720490

African (AFR) AF: 0.637 AC: 21171 AN: 33236

American (AMR) AF: 0.889 AC: 39434 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 25371 AN: 25602

East Asian (EAS) AF: 0.619 AC: 24413 AN: 39456

South Asian (SAS) AF: 0.822 AC: 70363 AN: 85610

European-Finnish (FIN) AF: 0.992 AC: 52816 AN: 53222

Middle Eastern (MID) AF: 0.960 AC: 5491 AN: 5720

European-Non Finnish (NFE) AF: 0.994 AC: 1097208 AN: 1103724

Other (OTH) AF: 0.937 AC: 56162 AN: 59928

GnomAD4 genome AF: 0.867 AC: 131904 AN: 152118 Hom.: 59136 Cov.: 31 AF XY: 0.863 AC XY: 64181 AN XY: 74368

African (AFR) AF: 0.644 AC: 26683 AN: 41430

American (AMR) AF: 0.895 AC: 13676 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3120 AN: 5148

South Asian (SAS) AF: 0.810 AC: 3907 AN: 4824

European-Finnish (FIN) AF: 0.994 AC: 10549 AN: 10610

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67453 AN: 68034

Other (OTH) AF: 0.897 AC: 1892 AN: 2110

Alfa AF: 0.938 Hom.: 152665

Bravo AF: 0.850

TwinsUK AF: 0.995 AC: 3690

ALSPAC AF: 0.992 AC: 3822

ESP6500AA AF: 0.652 AC: 2580

ESP6500EA AF: 0.993 AC: 8250

ExAC AF: 0.901 AC: 108921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	8.4e-7	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		9.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.46
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.021	D;D
Polyphen		1.0	D;.
Vest4		0.48
MPC		0.32
ClinPred		0.020	T
GERP RS		5.8
Varity_R		0.22
gMVP		0.56
Mutation Taster		=71/29	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs9831516; hg19: chr3-69230061; COSMIC: COSV68330003;