10-68726568-T-G

Variant names:

• chr10-68726568-T-G
• rs1782322
• NM_018237.4:c.73+3991T>G

Variant summary

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

The NM_018237.4(CCAR1):​c.73+3991T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,952 control chromosomes in the GnomAD database, including 10,651 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 0.36 (10651 hom., cov: 30)
• Consequence: CCAR1 NM_018237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 8 publications found

Genes affected

CCAR1 (HGNC:24236): (cell division cycle and apoptosis regulator 1) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; nuclear receptor coactivator activity; and transcription corepressor activity. Involved in positive regulation of cell migration and positive regulation of cell population proliferation. Acts upstream of or within positive regulation of apoptotic process. Located in nuclear envelope lumen. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018237.4. 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
	CCAR1	NM_018237.4	MANE Select	c.73+3991T>G		intron	N/A	NP_060707.2
	CCAR1	NM_001282959.2		c.73+3991T>G		intron	N/A	NP_001269888.1	Q8IX12-2
	CCAR1	NM_001282960.2		c.73+3991T>G		intron	N/A	NP_001269889.1	Q8IX12-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCAR1	ENST00000265872.11	TSL:1 MANE Select	c.73+3991T>G		intron	N/A	ENSP00000265872.6	Q8IX12-1
	CCAR1	ENST00000543225.5	TSL:1	c.73+3991T>G		intron	N/A	ENSP00000438610.1	F5H2E6
	CCAR1	ENST00000536012.5	TSL:1	c.-468+5286T>G		intron	N/A	ENSP00000439642.1	F5H1H2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55068 AN: 151834 Hom.: 10650 Cov.: 30

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.362 AC: 55069 AN: 151952 Hom.: 10651 Cov.: 30 AF XY: 0.358 AC XY: 26598 AN XY: 74242

African (AFR) AF: 0.220 AC: 9131 AN: 41478

American (AMR) AF: 0.350 AC: 5330 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1623 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1884 AN: 5176

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4818

European-Finnish (FIN) AF: 0.360 AC: 3786 AN: 10528

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30461 AN: 67940

Other (OTH) AF: 0.394 AC: 831 AN: 2108

Alfa AF: 0.426 Hom.: 55327

Bravo AF: 0.360

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.88
DANN	Benign	0.50
PhyloP100		-0.30
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1782322; hg19: chr10-70486325;