Genetic Variant KIAA0040:c.*159C>A (chr1-175160555-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014656.3(KIAA0040):c.*159C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 701,348 control chromosomes in the GnomAD database, including 54,272 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 0.38 ( 11463 hom., cov: 32)

Exomes 𝑓: 0.39 ( 42809 hom. )

Consequence

KIAA0040
NM_014656.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

Publications

21 publications found

Variant links:

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0040 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 (MetaRNN=0.0017420352).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014656.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0040	NM_014656.3	MANE Select	c.*159C>A	3_prime_UTR	Exon 4 of 4	NP_055471.2
KIAA0040	NM_001162893.2		c.*159C>A	3_prime_UTR	Exon 5 of 5	NP_001156365.1
KIAA0040	NM_001162894.2		c.*159C>A	3_prime_UTR	Exon 4 of 4	NP_001156366.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0040	ENST00000423313.6	TSL:1 MANE Select	c.*159C>A	3_prime_UTR	Exon 4 of 4	ENSP00000462172.1
KIAA0040	ENST00000444639.5	TSL:1	c.*159C>A	3_prime_UTR	Exon 4 of 4	ENSP00000463734.1
KIAA0040	ENST00000545251.6	TSL:1	c.*159C>A	3_prime_UTR	Exon 3 of 3	ENSP00000464040.1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58063

AN:

151898

Hom.:

11442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.403

GnomAD4 exome

AF:

0.388

AC:

213163

AN:

549332

Hom.:

42809

Cov.:

AF XY:

0.391

AC XY:

111011

AN XY:

284202

show subpopulations

African (AFR)

AF:

0.328

AC:

4657

AN:

14182

American (AMR)

AF:

0.571

AC:

10195

AN:

17866

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

7418

AN:

14198

East Asian (EAS)

AF:

0.544

AC:

16950

AN:

31178

South Asian (SAS)

AF:

0.428

AC:

19265

AN:

45000

European-Finnish (FIN)

AF:

0.370

AC:

11405

AN:

30788

Middle Eastern (MID)

AF:

0.443

AC:

958

AN:

2162

European-Non Finnish (NFE)

AF:

0.358

AC:

130756

AN:

364756

Other (OTH)

AF:

0.396

AC:

11559

AN:

29202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6034

12068

18102

24136

30170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2056

4112

6168

8224

10280

<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:

0.382

AC:

58124

AN:

152016

Hom.:

11463

Cov.:

AF XY:

0.387

AC XY:

28745

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.335

AC:

13878

AN:

41456

American (AMR)

AF:

0.516

AC:

7884

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1820

AN:

3466

East Asian (EAS)

AF:

0.542

AC:

2797

AN:

5162

South Asian (SAS)

AF:

0.440

AC:

2122

AN:

4818

European-Finnish (FIN)

AF:

0.356

AC:

3770

AN:

10576

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.359

AC:

24425

AN:

67954

Other (OTH)

AF:

0.402

AC:

847

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1788

3575

5363

7150

8938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.379

Hom.:

47241

Bravo

AF:

0.398

TwinsUK

AF:

0.328

AC:

1217

ALSPAC

AF:

0.344

AC:

1326

ESP6500AA

AF:

0.323

AC:

447

ESP6500EA

AF:

0.362

AC:

1151

Asia WGS

AF:

0.463

AC:

1607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.6

(source)

DANN

Benign

0.52

FATHMM_MKL

Benign

0.31

MetaRNN

Benign

0.0017

PhyloP100

1.5

Vest4

0.11

MVP

0.28

GERP RS

4.5

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