rs78249505

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032130.3(FAM186B):c.2452C>T(p.Arg818Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,613,140 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R818Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

FAM186B
NM_032130.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.55

Publications

7 publications found

Variant links:

Genes affected

FAM186B (HGNC:25296): (family with sequence similarity 186 member B) This gene product is a member of the FAM186 family, however, its exact function is not known. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

FAM186B links:

PRPF40B (HGNC:25031): (pre-mRNA processing factor 40 homolog B) This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants. [provided by RefSeq, Aug 2014]

PRPF40B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028795302).

BP6

Variant 12-49588536-G-A is Benign according to our data. Variant chr12-49588536-G-A is described in ClinVar as Benign. ClinVar VariationId is 1561511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1658/152364) while in subpopulation AFR AF = 0.0377 (1567/41570). AF 95% confidence interval is 0.0361. There are 36 homozygotes in GnomAd4. There are 742 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032130.3. 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
	FAM186B	NM_032130.3	MANE Select	c.2452C>T	p.Arg818Trp	missense	Exon 6 of 7	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2794C>T		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2452C>T	p.Arg818Trp	missense	Exon 6 of 7	ENSP00000257894.2	Q8IYM0-1
FAM186B	ENST00000532262.5	TSL:1	c.1291C>T	p.Arg431Trp	missense	Exon 3 of 5	ENSP00000436995.1	A0A0C4DGG0
FAM186B	ENST00000548841.5	TSL:5	c.121C>T	p.Arg41Trp	missense	Exon 2 of 4	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1656

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00274

AC:

687

AN:

250436

AF XY:

0.00187

show subpopulations

Gnomad AFR exome

AF:

0.0377

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.00103

AC:

1505

AN:

1460776

Hom.:

Cov.:

AF XY:

0.000885

AC XY:

643

AN XY:

726592

show subpopulations

African (AFR)

AF:

0.0370

AC:

1239

AN:

33458

American (AMR)

AF:

0.00193

AC:

AN:

44574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.000105

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111456

Other (OTH)

AF:

0.00205

AC:

124

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

164

246

328

410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0109

AC:

1658

AN:

152364

Hom.:

Cov.:

AF XY:

0.00996

AC XY:

742

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0377

AC:

1567

AN:

41570

American (AMR)

AF:

0.00451

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68042

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

158

237

316

395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00425

Hom.:

Bravo

AF:

0.0121

ESP6500AA

AF:

0.0409

AC:

180

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00330

AC:

400

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

1.6

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.97

REVEL

Benign

0.092

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0040

Polyphen

0.022

Vest4

0.37

MVP

0.16

MPC

0.57

ClinPred

0.024

GERP RS

3.4

Varity_R

0.046

gMVP

0.11

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over