dbSNP rs197388: ENSG00000284830:n.222+428T>A (chr1-111754860-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000412270.1(ENSG00000284830):n.222+428T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,208 control chromosomes in the GnomAD database, including 6,598 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 0.26 ( 6596 hom., cov: 33)

Exomes 𝑓: 0.23 ( 2 hom. )

Consequence

ENSG00000284830
ENST00000412270.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.293

Publications

25 publications found

Variant links:

Genes affected

ENSG00000284830 (HGNC:):

ENSG00000284830 links:

INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

INKA2 links:

DDX20 (HGNC:2743): (DEAD-box helicase 20) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

DDX20 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 (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INKA2	NM_198926.2 link	c.12+841T>A		intron_variant	Intron 1 of 1		NP_945120.1
LOC101928718	NR_125963.1 link	n.222+428T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000284830	ENST00000412270.1 link	n.222+428T>A	intron_variant	Intron 1 of 2	1
INKA2	ENST00000444059.2 link	n.124+841T>A	intron_variant	Intron 1 of 1	1
ENSG00000284830	ENST00000625113.1 link	n.678T>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
DDX20	ENST00000679724.1 link	c.-64A>T	5_prime_UTR_variant	Exon 1 of 12		ENSP00000505857.1	Q9UHI6-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39463

AN:

152060

Hom.:

6585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0402

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.233

AC:

AN:

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

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:

0.260

AC:

39529

AN:

152178

Hom.:

6596

Cov.:

AF XY:

0.254

AC XY:

18875

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.479

AC:

19860

AN:

41474

American (AMR)

AF:

0.154

AC:

2357

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

476

AN:

3472

East Asian (EAS)

AF:

0.0401

AC:

208

AN:

5192

South Asian (SAS)

AF:

0.136

AC:

657

AN:

4826

European-Finnish (FIN)

AF:

0.215

AC:

2273

AN:

10592

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

12969

AN:

68006

Other (OTH)

AF:

0.246

AC:

519

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1382

2764

4145

5527

6909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.238

Hom.:

653

Bravo

AF:

0.265

Asia WGS

AF:

0.111

AC:

385

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

2.3

(source)

DANN

Benign

0.77

PhyloP100

-0.29

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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