Genetic Variant KCTD19:c.1590+30A>G (chr16-67294550-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001100915.3(KCTD19):c.1590+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,494,894 control chromosomes in the GnomAD database, including 18,837 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 0.22 ( 7686 hom., cov: 32)

Exomes 𝑓: 0.094 ( 11151 hom. )

Consequence

KCTD19
NM_001100915.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

19 publications found

Variant links:

Genes affected

KCTD19 (HGNC:24753): (potassium channel tetramerization domain containing 19) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

KCTD19 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD19	NM_001100915.3	MANE Select	c.1590+30A>G		intron	N/A	NP_001094385.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCTD19	ENST00000304372.6	TSL:1 MANE Select	c.1590+30A>G	intron	N/A	ENSP00000305702.5
KCTD19	ENST00000570049.5	TSL:1	n.3422+30A>G	intron	N/A
KCTD19	ENST00000566392.5	TSL:2	n.2859+30A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33856

AN:

152024

Hom.:

7649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.0760

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.00481

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.0740

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.119

AC:

29444

AN:

248402

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.0659

Gnomad ASJ exome

AF:

0.0687

Gnomad EAS exome

AF:

0.00390

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.0786

Gnomad OTH exome

AF:

0.0960

GnomAD4 exome

AF:

0.0940

AC:

126188

AN:

1342752

Hom.:

11151

Cov.:

AF XY:

0.0937

AC XY:

63172

AN XY:

674108

show subpopulations

African (AFR)

AF:

0.608

AC:

19017

AN:

31268

American (AMR)

AF:

0.0699

AC:

3107

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

1813

AN:

25396

East Asian (EAS)

AF:

0.00263

AC:

103

AN:

39156

South Asian (SAS)

AF:

0.148

AC:

12417

AN:

83824

European-Finnish (FIN)

AF:

0.140

AC:

7443

AN:

53228

Middle Eastern (MID)

AF:

0.154

AC:

854

AN:

5544

European-Non Finnish (NFE)

AF:

0.0747

AC:

74956

AN:

1003512

Other (OTH)

AF:

0.115

AC:

6478

AN:

56390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5385

10770

16156

21541

26926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2898

5796

8694

11592

14490

<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:

0.223

AC:

33939

AN:

152142

Hom.:

7686

Cov.:

AF XY:

0.221

AC XY:

16466

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.584

AC:

24231

AN:

41470

American (AMR)

AF:

0.112

AC:

1720

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3468

East Asian (EAS)

AF:

0.00482

AC:

AN:

5182

South Asian (SAS)

AF:

0.143

AC:

688

AN:

4822

European-Finnish (FIN)

AF:

0.147

AC:

1556

AN:

10584

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0740

AC:

5033

AN:

68002

Other (OTH)

AF:

0.167

AC:

354

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

944

1889

2833

3778

4722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.113

Hom.:

1513

Bravo

AF:

0.233

Asia WGS

AF:

0.124

AC:

433

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.36

(source)

DANN

Benign

0.38

PhyloP100

-1.0

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