Genetic Variant ENST00000539338.6:n.4017T>G (chr17-39175092-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000539338.6(CACNB1):n.4017T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000246 in 814,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

CACNB1
ENST00000539338.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.420

Publications

16 publications found

Variant links:

Genes affected

CACNB1 (HGNC:1401): (calcium voltage-gated channel auxiliary subunit beta 1) The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

CACNB1 links:

ENSG00000266101 (HGNC:58562):

ENSG00000266101 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB1	NM_000723.5 link	c.*101T>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000394303.8	NP_000714.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB1	ENST00000394303.8 link	c.*101T>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_000723.5	ENSP00000377840.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000246

AC:

AN:

814480

Hom.:

Cov.:

AF XY:

0.00000479

AC XY:

AN XY:

417392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19842

American (AMR)

AF:

0.00

AC:

AN:

27660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16406

East Asian (EAS)

AF:

0.00

AC:

AN:

36340

South Asian (SAS)

AF:

0.00

AC:

AN:

58660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2688

European-Non Finnish (NFE)

AF:

0.00000352

AC:

AN:

568694

Other (OTH)

AF:

0.00

AC:

AN:

37894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

107

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.2

(source)

DANN

Benign

0.74

PhyloP100

0.42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over