rs4656940

Positions:

• chr1-160860478-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016382.4(CD244):​c.61+2139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,040 control chromosomes in the GnomAD database, including 5,511 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 0.26 (5511 hom., cov: 32)
• Consequence: CD244 NM_016382.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

CD244 (HGNC:18171): (CD244 molecule) This gene encodes a cell surface receptor expressed on natural killer (NK) cells (and some T cells) that mediate non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD244	NM_016382.4	c.61+2139T>C		intron_variant		ENST00000368034.9	NP_057466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD244	ENST00000368034.9	c.61+2139T>C		intron_variant		1	NM_016382.4	ENSP00000357013	P2
CD244	ENST00000322302.7	c.61+2139T>C		intron_variant		1		ENSP00000313619
CD244	ENST00000368033.7	c.61+2139T>C		intron_variant		1		ENSP00000357012	A2
CD244	ENST00000492063.5	c.61+2139T>C		intron_variant, NMD_transcript_variant		2		ENSP00000432636

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38786 AN: 151922 Hom.: 5508 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.255 AC: 38826 AN: 152040 Hom.: 5511 Cov.: 32 AF XY: 0.257 AC XY: 19095 AN XY: 74354

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.246

Alfa AF: 0.220 Hom.: 1888

Bravo AF: 0.260

Asia WGS AF: 0.404 AC: 1407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs4656940; hg19: chr1-160830268;