dbSNP rs1057302: KIAA0040:c.*3427T>C (chr1-175157287-A-G) – 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.*3427T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,110 control chromosomes in the GnomAD database, including 11,210 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 0.37 ( 11207 hom., cov: 32)

Exomes 𝑓: 0.70 ( 3 hom. )

Consequence

KIAA0040
NM_014656.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

16 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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0040	NM_014656.3 link	c.*3427T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000423313.6	NP_055471.2	Q15053

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA0040	ENST00000423313.6 link	c.*3427T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_014656.3	ENSP00000462172.1	Q15053
KIAA0040	ENST00000444639.5 link	c.*3427T>C	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000463734.1	Q15053
KIAA0040	ENST00000619513.1 link	c.*2882T>C	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000478803.1	A0A384DVV8

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56427

AN:

151982

Hom.:

11203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.0995

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.358

GnomAD4 exome

AF:

0.700

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.371

AC:

56448

AN:

152100

Hom.:

11207

Cov.:

AF XY:

0.369

AC XY:

27467

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.279

AC:

11587

AN:

41480

American (AMR)

AF:

0.314

AC:

4802

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3468

East Asian (EAS)

AF:

0.0995

AC:

514

AN:

5166

South Asian (SAS)

AF:

0.246

AC:

1188

AN:

4826

European-Finnish (FIN)

AF:

0.500

AC:

5286

AN:

10566

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30857

AN:

67984

Other (OTH)

AF:

0.359

AC:

759

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.385

Hom.:

4173

Bravo

AF:

0.351

Asia WGS

AF:

0.200

AC:

695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.5

(source)

DANN

Benign

0.50

PhyloP100

1.1

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