rs61746445

Variant names:

• chr4-17709587-G-A
• rs61746445
• NM_015688.2:c.199C>T

Variant summary

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

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2654690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015688.2. 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
	FAM184B	NM_015688.2	MANE Select	c.199C>T	p.Arg67Trp	missense	Exon 2 of 18	NP_056503.1	Q9ULE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM184B	ENST00000265018.4	TSL:1 MANE Select	c.199C>T	p.Arg67Trp	missense	Exon 2 of 18	ENSP00000265018.3	Q9ULE4
	FAM184B	ENST00000954035.1		c.199C>T	p.Arg67Trp	missense	Exon 2 of 17	ENSP00000624094.1

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

GnomAD2 exomes AF: 0.00254 AC: 364 AN: 143202 AF XY: 0.00268

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 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

African (AFR) AF: 0.000415 AC: 13 AN: 31338

American (AMR) AF: 0.00103 AC: 36 AN: 34828

Ashkenazi Jewish (ASJ) AF: 0.00801 AC: 198 AN: 24712

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35726

South Asian (SAS) AF: 0.00383 AC: 300 AN: 78258

European-Finnish (FIN) AF: 0.000914 AC: 44 AN: 48148

Middle Eastern (MID) AF: 0.0117 AC: 61 AN: 5196

European-Non Finnish (NFE) AF: 0.00269 AC: 2898 AN: 1077028

Other (OTH) AF: 0.00388 AC: 224 AN: 57734

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

African (AFR) AF: 0.000361 AC: 15 AN: 41580

American (AMR) AF: 0.00163 AC: 25 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4830

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00317 AC: 216 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00284 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.9
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
Mutation Taster		=94/6	polymorphism

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: rs61746445; hg19: chr4-17711210; COSMIC: COSV109412168;