rs7761436

Variant names:

• chr6-110181628-A-G
• rs7761436
• NM_015891.3:c.189+995A>G

Variant summary

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

The NM_015891.3(CDC40):​c.189+995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,166 control chromosomes in the GnomAD database, including 22,967 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 (22967 hom., cov: 32)
• Consequence: CDC40 NM_015891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 8 publications found

Genes affected

CDC40 (HGNC:17350): (cell division cycle 40) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]

CDC40 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 15

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015891.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC40	NM_015891.3	MANE Select	c.189+995A>G		intron	N/A	NP_056975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC40	ENST00000307731.2	TSL:1 MANE Select	c.189+995A>G		intron	N/A	ENSP00000304370.1
	CDC40	ENST00000924587.1		c.189+995A>G		intron	N/A	ENSP00000594646.1
	CDC40	ENST00000368932.5	TSL:5	c.189+995A>G		intron	N/A	ENSP00000357928.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76286 AN: 152048 Hom.: 22980 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.501 AC: 76260 AN: 152166 Hom.: 22967 Cov.: 32 AF XY: 0.505 AC XY: 37540 AN XY: 74382

African (AFR) AF: 0.142 AC: 5905 AN: 41520

American (AMR) AF: 0.570 AC: 8714 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3027 AN: 5168

South Asian (SAS) AF: 0.585 AC: 2824 AN: 4824

European-Finnish (FIN) AF: 0.660 AC: 6987 AN: 10588

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 45044 AN: 67988

Other (OTH) AF: 0.535 AC: 1131 AN: 2114

Alfa AF: 0.543 Hom.: 22377

Bravo AF: 0.477

Asia WGS AF: 0.570 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.41
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: rs7761436; hg19: chr6-110502831;