chr9-137878161-C-T

Variant names:

• chr9-137878161-C-T
• rs139719558
• NM_000718.4:c.228C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000718.4(CACNA1B):​c.228C>T​(p.Phe76Phe) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1B NM_000718.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

Genes affected

CACNA1B (HGNC:1389): (calcium voltage-gated channel subunit alpha1 B) The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ENSG00000203987 (HGNC:58213):

LOC100133077 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1B	NM_000718.4	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 47	ENST00000371372.6	NP_000709.1
CACNA1B	NM_001243812.2	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 47		NP_001230741.1
LOC100133077	NR_121583.1	n.2692-2481G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1B	ENST00000371372.6	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 47	5	NM_000718.4	ENSP00000360423.1
CACNA1B	ENST00000371357.5	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 46	5		ENSP00000360408.1
CACNA1B	ENST00000371363.5	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 46	5		ENSP00000360414.1
CACNA1B	ENST00000277551.6	c.228C>T	p.Phe76Phe	synonymous_variant	Exon 1 of 47	5		ENSP00000277551.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000122 AC: 3 AN: 245602 Hom.: 0 AF XY: 0.0000150 AC XY: 2 AN XY: 133610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1152904 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 555594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139719558; hg19: chr9-140772613;