dbSNP rs2272784: KIAA0040:c.-457C>A (chr1-175192713-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.-457C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,908 control chromosomes in the GnomAD database, including 18,660 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 0.49 ( 18630 hom., cov: 30)

Exomes 𝑓: 0.57 ( 30 hom. )

Consequence

KIAA0040
NM_014656.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0520

Publications

8 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 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.-457C>A	5_prime_UTR	Exon 1 of 4	NP_055471.2
KIAA0040	NM_001162893.2		c.-457C>A	5_prime_UTR	Exon 2 of 5	NP_001156365.1
KIAA0040	NM_001162895.2		c.-383C>A	5_prime_UTR	Exon 1 of 3	NP_001156367.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0040	ENST00000423313.6	TSL:1 MANE Select	c.-457C>A	5_prime_UTR	Exon 1 of 4	ENSP00000462172.1
KIAA0040	ENST00000545251.6	TSL:1	c.-383C>A	5_prime_UTR	Exon 1 of 3	ENSP00000464040.1
KIAA0040	ENST00000444639.5	TSL:1	c.-384+147C>A	intron	N/A	ENSP00000463734.1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74091

AN:

151622

Hom.:

18637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.571

AC:

AN:

168

Hom.:

Cov.:

AF XY:

0.536

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.556

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.593

AC:

AN:

118

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.488

AC:

74099

AN:

151740

Hom.:

18630

Cov.:

AF XY:

0.489

AC XY:

36250

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.382

AC:

15796

AN:

41376

American (AMR)

AF:

0.407

AC:

6212

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3468

East Asian (EAS)

AF:

0.425

AC:

2178

AN:

5128

South Asian (SAS)

AF:

0.527

AC:

2537

AN:

4810

European-Finnish (FIN)

AF:

0.600

AC:

6293

AN:

10494

Middle Eastern (MID)

AF:

0.524

AC:

153

AN:

292

European-Non Finnish (NFE)

AF:

0.560

AC:

38009

AN:

67874

Other (OTH)

AF:

0.489

AC:

1033

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1858

3716

5574

7432

9290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.528

Hom.:

34073

Bravo

AF:

0.464

Asia WGS

AF:

0.466

AC:

1618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

(source)

DANN

Benign

0.72

PhyloP100

-0.052

PromoterAI

-0.078

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=298/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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