12-9126085-A-G

Variant names:

• chr12-9126085-A-G
• rs7305636
• ENST00000839050.1:n.80+649A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000839050.1(ENSG00000309149):​n.80+649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,128 control chromosomes in the GnomAD database, including 5,675 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 (5675 hom., cov: 33)
• Consequence: ENSG00000309149 ENST00000839050.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 4 publications found

Genes affected

ENSG00000309149 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG1	XM_017018684.2	c.*34-9001A>G		intron_variant	Intron 6 of 6		XP_016874173.1
KLRG1	XM_017018685.2	c.*33+67919A>G		intron_variant	Intron 6 of 6		XP_016874174.1
KLRG1	XM_047428074.1	c.*33+67919A>G		intron_variant	Intron 6 of 6		XP_047284030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000309149	ENST00000839050.1	n.80+649A>G		intron_variant	Intron 1 of 1
ENSG00000309149	ENST00000839052.1	n.448+649A>G		intron_variant	Intron 1 of 1
ENSG00000309200	ENST00000839522.1	n.492-642T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38920 AN: 152010 Hom.: 5670 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.256 AC: 38947 AN: 152128 Hom.: 5675 Cov.: 33 AF XY: 0.258 AC XY: 19159 AN XY: 74376

African (AFR) AF: 0.134 AC: 5563 AN: 41504

American (AMR) AF: 0.335 AC: 5115 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3472

East Asian (EAS) AF: 0.0642 AC: 333 AN: 5188

South Asian (SAS) AF: 0.207 AC: 999 AN: 4828

European-Finnish (FIN) AF: 0.358 AC: 3776 AN: 10552

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21547 AN: 67986

Other (OTH) AF: 0.251 AC: 530 AN: 2110

Alfa AF: 0.297 Hom.: 908

Bravo AF: 0.247

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.52
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs7305636; hg19: chr12-9278681;