rs4656940

Variant names:

• chr1-160860478-A-G
• rs4656940
• NM_016382.4:c.61+2139T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016382.4. 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
	CD244	NM_016382.4	MANE Select	c.61+2139T>C		intron	N/A	NP_057466.1	Q9BZW8-2
	CD244	NM_001166663.2		c.61+2139T>C		intron	N/A	NP_001160135.1	Q9BZW8-1
	CD244	NM_001166664.2		c.61+2139T>C		intron	N/A	NP_001160136.1	Q9BZW8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD244	ENST00000368034.9	TSL:1 MANE Select	c.61+2139T>C		intron	N/A	ENSP00000357013.4	Q9BZW8-2
	CD244	ENST00000368033.7	TSL:1	c.61+2139T>C		intron	N/A	ENSP00000357012.3	Q9BZW8-1
	CD244	ENST00000322302.7	TSL:1	c.61+2139T>C		intron	N/A	ENSP00000313619.7	Q9BZW8-4

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

African (AFR) AF: 0.360 AC: 14932 AN: 41438

American (AMR) AF: 0.226 AC: 3453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2077 AN: 5172

South Asian (SAS) AF: 0.341 AC: 1649 AN: 4830

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10560

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13365 AN: 67978

Other (OTH) AF: 0.246 AC: 520 AN: 2116

Alfa AF: 0.237 Hom.: 4876

Bravo AF: 0.260

Asia WGS AF: 0.404 AC: 1407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.34
DANN	Benign	0.57
PhyloP100		-0.38
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: rs4656940; hg19: chr1-160830268;