NM_005810.4:c.*1044A>G

Variant names:

• chr12-9010581-A-G
• rs1805672
• NM_005810.4:c.*1044A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005810.4(KLRG1):​c.*1044A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,158 control chromosomes in the GnomAD database, including 4,863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4860 hom., cov: 32)
  • Exomes 𝑓: 0.23 (3 hom.)
• Consequence: KLRG1 NM_005810.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120
• Publications: 17 publications found

Genes affected

KLRG1 (HGNC:6380): (killer cell lectin like receptor G1) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-9010581-A-G is Benign according to our data. Variant chr12-9010581-A-G is described in ClinVar as Benign. ClinVar VariationId is 1279791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005810.4. 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
	KLRG1	NM_005810.4	MANE Select	c.*1044A>G		3_prime_UTR	Exon 5 of 5	NP_005801.3
	KLRG1	NM_001329099.2		c.*553A>G		3_prime_UTR	Exon 6 of 6	NP_001316028.1	Q96E93-1
	KLRG1	NM_001329101.2		c.*1044A>G		3_prime_UTR	Exon 5 of 5	NP_001316030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG1	ENST00000356986.8	TSL:1 MANE Select	c.*1044A>G		3_prime_UTR	Exon 5 of 5	ENSP00000349477.3	Q96E93-2
	KLRG1	ENST00000266551.8	TSL:1	c.*553A>G		3_prime_UTR	Exon 6 of 6	ENSP00000266551.4	Q96E93-1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35419 AN: 151930 Hom.: 4855 Cov.: 32

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.227 AC: 25 AN: 110 Hom.: 3 Cov.: 0 AF XY: 0.212 AC XY: 14 AN XY: 66

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.333 AC: 2 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.233 AC: 21 AN: 90

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.233 AC: 35432 AN: 152048 Hom.: 4860 Cov.: 32 AF XY: 0.233 AC XY: 17326 AN XY: 74320

African (AFR) AF: 0.0746 AC: 3098 AN: 41508

American (AMR) AF: 0.310 AC: 4733 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1112 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1895 AN: 5158

South Asian (SAS) AF: 0.323 AC: 1555 AN: 4814

European-Finnish (FIN) AF: 0.256 AC: 2709 AN: 10566

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19489 AN: 67958

Other (OTH) AF: 0.267 AC: 563 AN: 2112

Alfa AF: 0.271 Hom.: 6099

Bravo AF: 0.232

Asia WGS AF: 0.348 AC: 1207 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.80
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1805672; hg19: chr12-9163177;