19-11152974-G-T

Variant names:

• chr19-11152974-G-T
• rs892115
• NM_182513.4:c.160+2643C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182513.4(SPC24):​c.160+2643C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,482 control chromosomes in the GnomAD database, including 28,511 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 0.60 (28511 hom., cov: 28)
• Consequence: SPC24 NM_182513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 17 publications found

Genes affected

SPC24 (HGNC:26913): (SPC24 component of NDC80 kinetochore complex) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. Part of Ndc80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC24	NM_182513.4	MANE Select	c.160+2643C>A		intron	N/A	NP_872319.1
	SPC24	NM_001317031.2		c.160+2643C>A		intron	N/A	NP_001303960.1
	SPC24	NM_001394314.1		c.160+2643C>A		intron	N/A	NP_001381243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPC24	ENST00000592540.6	TSL:1 MANE Select	c.160+2643C>A		intron	N/A	ENSP00000465075.1
	SPC24	ENST00000585567.5	TSL:3	c.160+2643C>A		intron	N/A	ENSP00000468818.1
	SPC24	ENST00000591396.5	TSL:5	c.148+2643C>A		intron	N/A	ENSP00000466688.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91400 AN: 151362 Hom.: 28519 Cov.: 28

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.604 AC: 91429 AN: 151482 Hom.: 28511 Cov.: 28 AF XY: 0.602 AC XY: 44539 AN XY: 74022

African (AFR) AF: 0.449 AC: 18541 AN: 41286

American (AMR) AF: 0.632 AC: 9562 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2297 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1917 AN: 5122

South Asian (SAS) AF: 0.578 AC: 2771 AN: 4792

European-Finnish (FIN) AF: 0.663 AC: 6977 AN: 10528

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47403 AN: 67866

Other (OTH) AF: 0.620 AC: 1294 AN: 2088

Alfa AF: 0.656 Hom.: 84529

Bravo AF: 0.589

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.40
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892115; hg19: chr19-11263650;