chr12-49587939-T-C

Position:

• chr12-49587939-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032130.3(FAM186B):​c.2535-187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,176 control chromosomes in the GnomAD database, including 3,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (3585 hom., cov: 32)
• Consequence: FAM186B NM_032130.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.135

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-49587939-T-C is Benign according to our data. Variant chr12-49587939-T-C is described in ClinVar as [Benign]. Clinvar id is 1278850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186B	NM_032130.3	c.2535-187A>G		intron_variant		ENST00000257894.2	NP_115506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186B	ENST00000257894.2	c.2535-187A>G		intron_variant		1	NM_032130.3	ENSP00000257894	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27897 AN: 152058 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 27972 AN: 152176 Hom.: 3585 Cov.: 32 AF XY: 0.182 AC XY: 13571 AN XY: 74420

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.0991

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0811 Hom.: 176

Bravo AF: 0.191

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs7977389; hg19: chr12-49981722;