Genetic Variant NM_001145475.3:c.6520C>T (chr12-50334087-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001145475.3(FAM186A):c.6520C>T(p.Arg2174*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00911 in 1,543,834 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0085 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 99 hom. )

Consequence

FAM186A
NM_001145475.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

Publications

6 publications found

Variant links:

Genes affected

FAM186A (HGNC:26980): (family with sequence similarity 186 member A)

FAM186A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 12-50334087-G-A is Benign according to our data. Variant chr12-50334087-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3387945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145475.3. 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
	FAM186A	NM_001145475.3	MANE Select	c.6520C>T	p.Arg2174*	stop_gained	Exon 5 of 8	NP_001138947.1	A6NE01

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM186A	ENST00000327337.6	TSL:5 MANE Select	c.6520C>T	p.Arg2174*	stop_gained	Exon 5 of 8	ENSP00000329995.5	A6NE01
FAM186A	ENST00000543111.5	TSL:5	c.6520C>T	p.Arg2174*	stop_gained	Exon 5 of 8	ENSP00000441337.1	F5GYN0
FAM186A	ENST00000539751.1	TSL:5	n.16C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000437706.1	H0YFA1

Frequencies

GnomAD3 genomes

AF:

0.00851

AC:

1292

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00814

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00849

Gnomad OTH

AF:

0.00480

GnomAD2 exomes

AF:

0.0103

AC:

1502

AN:

145504

AF XY:

0.00974

show subpopulations

Gnomad AFR exome

AF:

0.00182

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0396

Gnomad NFE exome

AF:

0.00912

Gnomad OTH exome

AF:

0.00708

GnomAD4 exome

AF:

0.00917

AC:

12765

AN:

1391836

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

6181

AN XY:

686244

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

31108

American (AMR)

AF:

0.00494

AC:

166

AN:

33612

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

317

AN:

24886

East Asian (EAS)

AF:

0.0000281

AC:

AN:

35616

South Asian (SAS)

AF:

0.00379

AC:

294

AN:

77474

European-Finnish (FIN)

AF:

0.0383

AC:

1886

AN:

49204

Middle Eastern (MID)

AF:

0.00318

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.00885

AC:

9530

AN:

1076608

Other (OTH)

AF:

0.00902

AC:

520

AN:

57662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

554

1108

1663

2217

2771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00851

AC:

1293

AN:

151998

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

750

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

41466

American (AMR)

AF:

0.00813

AC:

124

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00333

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.0438

AC:

461

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00850

AC:

578

AN:

67984

Other (OTH)

AF:

0.00475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00756

Hom.:

Bravo

AF:

0.00547

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.0101

AC:

ExAC

AF:

0.00772

AC:

184

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.0092

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.053

PhyloP100

1.1

Vest4

0.26

GERP RS

0.38

Mutation Taster

=186/14

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over