1-160841211-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016382.4(CD244):c.654G>T(p.Gln218His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: CD244 NM_016382.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001044
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023406416).
• BP6: Variant 1-160841211-C-A is Benign according to our data. Variant chr1-160841211-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2207348.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD244	NM_016382.4	c.654G>T	p.Gln218His	missense_variant, splice_region_variant	3/9	ENST00000368034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD244	ENST00000368034.9	c.654G>T	p.Gln218His	missense_variant, splice_region_variant	3/9	1	NM_016382.4	P2
CD244	ENST00000368033.7	c.669G>T	p.Gln223His	missense_variant, splice_region_variant	3/9	1		A2
CD244	ENST00000322302.7	c.379+373G>T		intron_variant		1
CD244	ENST00000492063.5	c.654G>T	p.Gln218His	missense_variant, splice_region_variant, NMD_transcript_variant	3/9	2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000398 AC: 10 AN: 251202 Hom.: 0 AF XY: 0.0000589 AC XY: 8 AN XY: 135768

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1461790 Hom.: 0 Cov.: 33 AF XY: 0.0000371 AC XY: 27 AN XY: 727196

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 13 AN XY: 74516

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000500 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	1.6
Dann	Benign	0.86
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.028
Sift	Benign	0.59	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0070	B;B
Vest4		0.082
MutPred		0.37		.;Gain of loop (P = 0.1069);
MVP		0.14
MPC		0.064
ClinPred		0.018	T
GERP RS		0.30
Varity_R		0.063
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.022
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: rs184282870; hg19: chr1-160811001;