NM_001303618.2:c.46+30A>G

Variant names:

• chr18-69947331-T-C
• rs75418532
• NM_001303618.2:c.46+30A>G

Variant summary

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

The NM_001303618.2(CD226):​c.46+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00488 in 1,446,224 control chromosomes in the GnomAD database, including 261 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 0.024 (144 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (117 hom.)
• Consequence: CD226 NM_001303618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981
• Publications: 1 publications found

Genes affected

CD226 (HGNC:16961): (CD226 molecule) This gene encodes a glycoprotein expressed on the surface of NK cells, platelets, monocytes and a subset of T cells. It is a member of the Ig-superfamily containing 2 Ig-like domains of the V-set. The protein mediates cellular adhesion of platelets and megakaryocytic cells to vascular endothelial cells. The protein also plays a role in megakaryocytic cell maturation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303618.2. 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
	CD226	NM_001303618.2	MANE Select	c.46+30A>G		intron	N/A	NP_001290547.1
	CD226	NM_006566.4		c.46+30A>G		intron	N/A	NP_006557.2
	CD226	NM_001303619.2		c.-84+9424A>G		intron	N/A	NP_001290548.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD226	ENST00000582621.6	TSL:1 MANE Select	c.46+30A>G		intron	N/A	ENSP00000461947.1
	CD226	ENST00000280200.8	TSL:1	c.46+30A>G		intron	N/A	ENSP00000280200.4
	CD226	ENST00000581982.5	TSL:1	c.-84+9424A>G		intron	N/A	ENSP00000464084.1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3675 AN: 152114 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.00719 AC: 1531 AN: 212836 AF XY: 0.00525

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.00304

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.00690

GnomAD4 exome AF: 0.00260 AC: 3366 AN: 1293992 Hom.: 117 Cov.: 18 AF XY: 0.00238 AC XY: 1552 AN XY: 650828

African (AFR) AF: 0.0841 AC: 2377 AN: 28272

American (AMR) AF: 0.00650 AC: 205 AN: 31534

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 63 AN: 23162

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.000172 AC: 13 AN: 75784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52440

Middle Eastern (MID) AF: 0.00702 AC: 36 AN: 5130

European-Non Finnish (NFE) AF: 0.000365 AC: 359 AN: 984844

Other (OTH) AF: 0.00577 AC: 313 AN: 54272

GnomAD4 genome AF: 0.0243 AC: 3693 AN: 152232 Hom.: 144 Cov.: 32 AF XY: 0.0231 AC XY: 1723 AN XY: 74442

African (AFR) AF: 0.0830 AC: 3445 AN: 41512

American (AMR) AF: 0.0101 AC: 155 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68032

Other (OTH) AF: 0.0180 AC: 38 AN: 2110

Alfa AF: 0.0129 Hom.: 19

Bravo AF: 0.0276

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.98
PromoterAI		0.0015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs75418532; hg19: chr18-67614567;