rs4804146

Variant names:

• chr19-11145500-C-T
• rs4804146
• NM_182513.4:c.*1683G>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.*1683G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,118 control chromosomes in the GnomAD database, including 48,918 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 0.80 (48909 hom., cov: 31)
  • Exomes 𝑓: 0.74 (9 hom.)
• Consequence: SPC24 NM_182513.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPC24	NM_182513.4	c.*1683G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000592540.6	NP_872319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPC24	ENST00000592540.6	c.*1683G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_182513.4	ENSP00000465075.1
SPC24	ENST00000585567.5	c.435+2370G>A		intron_variant	Intron 4 of 5	3		ENSP00000468818.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121332 AN: 151966 Hom.: 48881 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.836

GnomAD4 exome AF: 0.735 AC: 25 AN: 34 Hom.: 9 Cov.: 0 AF XY: 0.731 AC XY: 19 AN XY: 26

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.808 AC: 21 AN: 26

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.798 AC: 121416 AN: 152084 Hom.: 48909 Cov.: 31 AF XY: 0.801 AC XY: 59510 AN XY: 74324

African (AFR) AF: 0.691 AC: 28664 AN: 41468

American (AMR) AF: 0.876 AC: 13346 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3472

East Asian (EAS) AF: 0.732 AC: 3791 AN: 5178

South Asian (SAS) AF: 0.808 AC: 3888 AN: 4812

European-Finnish (FIN) AF: 0.853 AC: 9038 AN: 10600

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57384 AN: 68006

Other (OTH) AF: 0.833 AC: 1756 AN: 2108

Alfa AF: 0.821 Hom.: 103281

Bravo AF: 0.796

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.57
PhyloP100		-0.28
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: rs4804146; hg19: chr19-11256176;