rs147282399

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_032130.3(FAM186B):c.2507G>A(p.Arg836Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,613,176 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 8 hom. )

Consequence

FAM186B
NM_032130.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.21

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030449927).

BP6

Variant 12-49588481-C-T is Benign according to our data. Variant chr12-49588481-C-T is described in ClinVar as Benign. ClinVar VariationId is 1602150.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00489 (745/152382) while in subpopulation AFR AF = 0.017 (706/41594). AF 95% confidence interval is 0.0159. There are 4 homozygotes in GnomAd4. There are 341 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 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.2507G>A	p.Arg836Gln	missense	Exon 6 of 7	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2849G>A		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.2507G>A	p.Arg836Gln	missense	Exon 6 of 7	ENSP00000257894.2	Q8IYM0-1
FAM186B	ENST00000532262.5	TSL:1	c.1346G>A	p.Arg449Gln	missense	Exon 3 of 5	ENSP00000436995.1	A0A0C4DGG0
FAM186B	ENST00000548841.5	TSL:5	c.176G>A	p.Arg59Gln	missense	Exon 2 of 4	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes

AF:

0.00485

AC:

739

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00125

AC:

314

AN:

250430

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.000494

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000525

AC:

767

AN:

1460794

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

311

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.0191

AC:

639

AN:

33466

American (AMR)

AF:

0.000740

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86080

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53340

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111466

Other (OTH)

AF:

0.00118

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00489

AC:

745

AN:

152382

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.0170

AC:

706

AN:

41594

American (AMR)

AF:

0.00157

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68040

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00187

Hom.:

Bravo

AF:

0.00544

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00152

AC:

185

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0040

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.030

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.075

PhyloP100

-3.2

PrimateAI

Benign

0.17

PROVEAN

Benign

-1.5

REVEL

Benign

0.0090

Sift

Benign

0.29

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.11

MVP

0.014

MPC

0.15

ClinPred

0.00068

GERP RS

-7.8

Varity_R

0.026

gMVP

0.057

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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