Variant 12-49587695-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_032130.3(FAM186B):c.2592C>T(p.Tyr864=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,614,082 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 17 hom. )

Consequence

FAM186B
NM_032130.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.256

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 12-49587695-G-A is Benign according to our data. Variant chr12-49587695-G-A is described in ClinVar as [Benign]. Clinvar id is 2041514.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.256 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186B	NM_032130.3 linkuse as main transcript	c.2592C>T	p.Tyr864=	synonymous_variant	7/7	ENST00000257894.2	NP_115506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186B	ENST00000257894.2 linkuse as main transcript	c.2592C>T	p.Tyr864=	synonymous_variant	7/7	1	NM_032130.3	ENSP00000257894	P1	Q8IYM0-1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00223

AC:

559

AN:

251116

Hom.:

AF XY:

0.00220

AC XY:

298

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00358

AC:

5234

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00343

AC XY:

2491

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00446

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152226

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00423

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00217

EpiCase

AF:

0.00360

EpiControl

AF:

0.00391

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.9

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over