chr1-160839020-T-C

Position:

• chr1-160839020-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016382.4(CD244):​c.685A>G​(p.Ile229Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,928 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (22 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (15 hom.)
• Consequence: CD244 NM_016382.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.149

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00261271).
• BP6: Variant 1-160839020-T-C is Benign according to our data. Variant chr1-160839020-T-C is described in ClinVar as [Benign]. Clinvar id is 784959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00659 (1003/152278) while in subpopulation AFR AF= 0.0229 (953/41552). AF 95% confidence interval is 0.0217. There are 22 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD244	NM_016382.4	c.685A>G	p.Ile229Val	missense_variant	4/9	ENST00000368034.9	NP_057466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD244	ENST00000368034.9	c.685A>G	p.Ile229Val	missense_variant	4/9	1	NM_016382.4	ENSP00000357013	P2

Frequencies

GnomAD3 genomes AF: 0.00657 AC: 999 AN: 152160 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00169 AC: 424 AN: 250996 Hom.: 3 AF XY: 0.00124 AC XY: 168 AN XY: 135668

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000712 AC: 1041 AN: 1461650 Hom.: 15 Cov.: 30 AF XY: 0.000606 AC XY: 441 AN XY: 727138

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.000985

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00659 AC: 1003 AN: 152278 Hom.: 22 Cov.: 32 AF XY: 0.00630 AC XY: 469 AN XY: 74462

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00135 Hom.: 4

Bravo AF: 0.00765

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0195 AC: 86

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00211 AC: 256

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.081
DANN	Benign	0.20
DEOGEN2	Benign	0.12	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.42	T;T;T
MetaRNN	Benign	0.0026	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.0020
Sift	Benign	0.29	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.011	B;B;B
Vest4		0.079
MVP		0.055
MPC		0.057
ClinPred		0.0033	T
GERP RS		-4.4
Varity_R		0.021
gMVP		0.33

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: rs76030314; hg19: chr1-160808810;