NM_032130.3:c.2535-187A>G

Variant names:

• chr12-49587939-T-C
• rs7977389
• NM_032130.3:c.2535-187A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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.2535-187A>G		intron	N/A	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2876+515A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2535-187A>G		intron	N/A	ENSP00000257894.2	Q8IYM0-1
	FAM186B	ENST00000532262.5	TSL:1	c.1374-187A>G		intron	N/A	ENSP00000436995.1	A0A0C4DGG0
	FAM186B	ENST00000551047.5	TSL:5	c.634-3333A>G		intron	N/A	ENSP00000448656.1	F8VRJ5

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

African (AFR) AF: 0.371 AC: 15392 AN: 41482

American (AMR) AF: 0.127 AC: 1936 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.0743 AC: 385 AN: 5182

South Asian (SAS) AF: 0.0991 AC: 478 AN: 4824

European-Finnish (FIN) AF: 0.125 AC: 1331 AN: 10622

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7487 AN: 67988

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.0932 Hom.: 237

Bravo AF: 0.191

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.29
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7977389; hg19: chr12-49981722;