Genetic Variant FAM186A:p.Lys1954Lys (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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM186A	NM_001145475.3 link	c.5862A>G	p.Lys1954Lys	synonymous_variant	Exon 4 of 8	ENST00000327337.6	NP_001138947.1	A6NE01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM186A	ENST00000327337.6 link	c.5862A>G	p.Lys1954Lys	synonymous_variant	Exon 4 of 8	5	NM_001145475.3	ENSP00000329995.5	A6NE01
FAM186A	ENST00000543111.5 link	c.5862A>G	p.Lys1954Lys	synonymous_variant	Exon 4 of 8	5		ENSP00000441337.1	F5GYN0
FAM186A	ENST00000543096.5 link	c.-106A>G		upstream_gene_variant		2		ENSP00000443703.1	F5H8C1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over