rs153898

Positions:

• chr5-94852917-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024717.7(MCTP1):​c.2436+15416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,710 control chromosomes in the GnomAD database, including 22,805 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 (22805 hom., cov: 31)
• Consequence: MCTP1 NM_024717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

Genes affected

MCTP1 (HGNC:26183): (multiple C2 and transmembrane domain containing 1) Enables calcium ion binding activity. Predicted to be involved in several processes, including modulation of chemical synaptic transmission; negative regulation of endocytosis; and negative regulation of response to oxidative stress. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCTP1	NM_024717.7	c.2436+15416G>A		intron_variant		ENST00000515393.6	NP_078993.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCTP1	ENST00000515393.6	c.2436+15416G>A		intron_variant		1	NM_024717.7	ENSP00000424126.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75562 AN: 151592 Hom.: 22812 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.498 AC: 75558 AN: 151710 Hom.: 22805 Cov.: 31 AF XY: 0.489 AC XY: 36250 AN XY: 74124

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.567

Alfa AF: 0.668 Hom.: 44622

Bravo AF: 0.476

Asia WGS AF: 0.403 AC: 1393 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs153898; hg19: chr5-94188622; COSMIC: COSV56508749;