Genetic Variant NM_001145475.3:c.5862A>G (chr12-50350970-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001145475.3(FAM186A):c.5862A>G(p.Lys1954Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,551,106 control chromosomes in the GnomAD database, including 332,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 31525 hom., cov: 31)

Exomes 𝑓: 0.65 ( 301198 hom. )

Consequence

FAM186A
NM_001145475.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.450

Publications

19 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=0.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

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.5862A>G	p.Lys1954Lys	synonymous	Exon 4 of 8	NP_001138947.1	A6NE01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186A	ENST00000327337.6	TSL:5 MANE Select	c.5862A>G	p.Lys1954Lys	synonymous	Exon 4 of 8	ENSP00000329995.5	A6NE01
	FAM186A	ENST00000543111.5	TSL:5	c.5862A>G	p.Lys1954Lys	synonymous	Exon 4 of 8	ENSP00000441337.1	F5GYN0

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96847

AN:

151844

Hom.:

31490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.740

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.628

GnomAD2 exomes

AF:

0.670

AC:

102964

AN:

153622

AF XY:

0.656

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.705

Gnomad EAS exome

AF:

0.748

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.663

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.653

AC:

914173

AN:

1399144

Hom.:

301198

Cov.:

AF XY:

0.649

AC XY:

448062

AN XY:

690086

show subpopulations

African (AFR)

AF:

0.525

AC:

16585

AN:

31588

American (AMR)

AF:

0.772

AC:

27544

AN:

35660

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

17694

AN:

25172

East Asian (EAS)

AF:

0.754

AC:

26942

AN:

35738

South Asian (SAS)

AF:

0.522

AC:

41316

AN:

79192

European-Finnish (FIN)

AF:

0.740

AC:

36434

AN:

49248

Middle Eastern (MID)

AF:

0.598

AC:

3407

AN:

5698

European-Non Finnish (NFE)

AF:

0.655

AC:

707172

AN:

1078864

Other (OTH)

AF:

0.639

AC:

37079

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

19438

38876

58315

77753

97191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18640

37280

55920

74560

93200

<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:

0.638

AC:

96939

AN:

151962

Hom.:

31525

Cov.:

AF XY:

0.643

AC XY:

47799

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.534

AC:

22122

AN:

41418

American (AMR)

AF:

0.730

AC:

11132

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

2432

AN:

3470

East Asian (EAS)

AF:

0.740

AC:

3824

AN:

5168

South Asian (SAS)

AF:

0.509

AC:

2451

AN:

4816

European-Finnish (FIN)

AF:

0.750

AC:

7935

AN:

10580

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.660

AC:

44826

AN:

67952

Other (OTH)

AF:

0.629

AC:

1326

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1725

3450

5176

6901

8626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.650

Hom.:

47856

Bravo

AF:

0.636

Asia WGS

AF:

0.609

AC:

2115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.30

PhyloP100

0.45

PromoterAI

0.0068

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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