Variant 12-49599389-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032130.3(FAM186B):c.2171+80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,459,990 control chromosomes in the GnomAD database, including 536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 106 hom., cov: 31)

Exomes 𝑓: 0.023 ( 430 hom. )

Consequence

FAM186B
NM_032130.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.792

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-49599389-T-C is Benign according to our data. Variant chr12-49599389-T-C is described in ClinVar as [Benign]. Clinvar id is 1243969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186B	NM_032130.3 linkuse as main transcript	c.2171+80A>G		intron_variant		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.2171+80A>G		intron_variant		1	NM_032130.3	ENSP00000257894	P1	Q8IYM0-1

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4726

AN:

152166

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0591

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0363

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.0231

AC:

30153

AN:

1307706

Hom.:

430

AF XY:

0.0231

AC XY:

14668

AN XY:

634584

show subpopulations

Gnomad4 AFR exome

AF:

0.0608

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0375

Gnomad4 EAS exome

AF:

0.00441

Gnomad4 SAS exome

AF:

0.0322

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0312

AC:

4745

AN:

152284

Hom.:

106

Cov.:

AF XY:

0.0300

AC XY:

2235

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.00772

Gnomad4 SAS

AF:

0.0367

Gnomad4 FIN

AF:

0.00772

Gnomad4 NFE

AF:

0.0218

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

DANN

Benign

0.78

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