chr12-49587695-G-A

Variant names:

• chr12-49587695-G-A
• rs144159467
• NM_032130.3:c.2592C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_032130.3(FAM186B):​c.2592C>T​(p.Tyr864Tyr) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.256
• Publications: 4 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.019).
• BP6: Variant 12-49587695-G-A is Benign according to our data. Variant chr12-49587695-G-A is described in ClinVar as Benign. ClinVar VariationId 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

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.2592C>T	p.Tyr864Tyr	synonymous	Exon 7 of 7	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2876+759C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2592C>T	p.Tyr864Tyr	synonymous	Exon 7 of 7	ENSP00000257894.2	Q8IYM0-1
	FAM186B	ENST00000532262.5	TSL:1	c.1431C>T	p.Tyr477Tyr	synonymous	Exon 4 of 5	ENSP00000436995.1	A0A0C4DGG0
	FAM186B	ENST00000548841.5	TSL:5	c.261C>T	p.Tyr87Tyr	synonymous	Exon 3 of 4	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 329 AN: 152108 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00223 AC: 559 AN: 251116 AF XY: 0.00220

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 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.: 17 Cov.: 31 AF XY: 0.00343 AC XY: 2491 AN XY: 727236

African (AFR) AF: 0.000597 AC: 20 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86258

European-Finnish (FIN) AF: 0.000861 AC: 46 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00446 AC: 4957 AN: 1111988

Other (OTH) AF: 0.00260 AC: 157 AN: 60396

GnomAD4 genome AF: 0.00216 AC: 329 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74430

African (AFR) AF: 0.000746 AC: 31 AN: 41536

American (AMR) AF: 0.000392 AC: 6 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00423 AC: 288 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00217

EpiCase AF: 0.00360

EpiControl AF: 0.00391

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.9
DANN	Benign	0.76
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144159467; hg19: chr12-49981478; COSMIC: COSV57721579; COSMIC: COSV57721579;