rs61746445

chr4-17709587-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015688.2(FAM184B):c.199C>T(p.Arg67Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,545,308 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (15 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006183207).
• BP6: Variant 4-17709587-G-A is Benign according to our data. Variant chr4-17709587-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM184B	NM_015688.2	c.199C>T	p.Arg67Trp	missense_variant	2/18	ENST00000265018.4
FAM184B	XM_047450066.1	c.199C>T	p.Arg67Trp	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184B	ENST00000265018.4	c.199C>T	p.Arg67Trp	missense_variant	2/18	1	NM_015688.2	P1

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 307 AN: 152222 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00254 AC: 364 AN: 143202 Hom.: 3 AF XY: 0.00268 AC XY: 206 AN XY: 76752

Gnomad AFR exome AF: 0.000293

Gnomad AMR exome AF: 0.000902

Gnomad ASJ exome AF: 0.00762

Gnomad EAS exome AF: 0.0000956

Gnomad SAS exome AF: 0.00386

Gnomad FIN exome AF: 0.000743

Gnomad NFE exome AF: 0.00307

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00271 AC: 3775 AN: 1392968 Hom.: 15 Cov.: 35 AF XY: 0.00282 AC XY: 1935 AN XY: 686998

Gnomad4 AFR exome AF: 0.000415

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00801

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00383

Gnomad4 FIN exome AF: 0.000914

Gnomad4 NFE exome AF: 0.00269

Gnomad4 OTH exome AF: 0.00388

GnomAD4 genome AF: 0.00202 AC: 307 AN: 152340 Hom.: 1 Cov.: 33 AF XY: 0.00201 AC XY: 150 AN XY: 74490

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00317

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00305 Hom.: 2

Bravo AF: 0.00211

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00234 AC: 9

ExAC AF: 0.00240 AC: 77

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

FAM184B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.044
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.36
ClinPred		0.045	T
GERP RS		1.1
Varity_R		0.34
gMVP		0.41

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: rs61746445; hg19: chr4-17711210;