dbSNP rs768963: CACTIN:c.1163-820C>T (chr19-3615409-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001080543.2(CACTIN):c.1163-820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 153,362 control chromosomes in the GnomAD database, including 20,424 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 0.50 ( 20180 hom., cov: 33)

Exomes 𝑓: 0.58 ( 244 hom. )

Consequence

CACTIN
NM_001080543.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Variant links:

Genes affected

CACTIN (HGNC:29938): (cactin, spliceosome C complex subunit) Enables RNA binding activity. Involved in several processes, including cellular response to cytokine stimulus; negative regulation of cytokine production; and negative regulation of signal transduction. Located in cytosol and nuclear speck. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

CACTIN 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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CACTIN	NM_001080543.2 link	c.1163-820C>T	intron_variant	Intron 6 of 9	ENST00000429344.7	NP_001074012.1	Q8WUQ7-1
CACTIN	XM_011528161.3 link	c.*2421C>T	3_prime_UTR_variant	Exon 7 of 7		XP_011526463.1
CACTIN	NM_021231.2 link	c.1163-820C>T	intron_variant	Intron 6 of 10		NP_067054.1	Q8WUQ7-1
CACTIN	XM_011528160.3 link	c.1163-820C>T	intron_variant	Intron 6 of 7		XP_011526462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACTIN	ENST00000429344.7 link	c.1163-820C>T		intron_variant	Intron 6 of 9	1	NM_001080543.2	ENSP00000415078.1		Q8WUQ7-1

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76544

AN:

151928

Hom.:

20191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.550

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.543

GnomAD4 exome

AF:

0.580

AC:

763

AN:

1316

Hom.:

244

Cov.:

AF XY:

0.564

AC XY:

500

AN XY:

886

show subpopulations

African (AFR)

AF:

0.357

AC:

AN:

American (AMR)

AF:

0.706

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AF:

0.479

AC:

AN:

European-Finnish (FIN)

AF:

0.617

AC:

AN:

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.590

AC:

604

AN:

1024

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.503

AC:

76555

AN:

152046

Hom.:

20180

Cov.:

AF XY:

0.505

AC XY:

37526

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.355

AC:

14709

AN:

41436

American (AMR)

AF:

0.584

AC:

8932

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1953

AN:

3470

East Asian (EAS)

AF:

0.334

AC:

1723

AN:

5154

South Asian (SAS)

AF:

0.422

AC:

2029

AN:

4810

European-Finnish (FIN)

AF:

0.604

AC:

6403

AN:

10608

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

39006

AN:

67954

Other (OTH)

AF:

0.536

AC:

1130

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1887

3774

5661

7548

9435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.524

Hom.:

2672

Bravo

AF:

0.499

Asia WGS

AF:

0.391

AC:

1363

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.42

(source)

DANN

Benign

0.45

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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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rs768963

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over