rs1977656

chr6-149971605-G-Cchr6-149971605-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025218.4(ULBP1):c.*259G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 157,276 control chromosomes in the GnomAD database, including 2,171 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 0.13 (2162 hom., cov: 32)
  • Exomes 𝑓: 0.026 (9 hom.)
• Consequence: ULBP1 NM_025218.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

Genes affected

ULBP1 (HGNC:14893): (UL16 binding protein 1) The protein encoded by this gene is a ligand of natural killer group 2, member D (NKG2D), an immune system-activating receptor on NK cells and T-cells. Binding of the encoded ligand to NKG2D leads to activation of several signal transduction pathways, including those of JAK2, STAT5, ERK and PI3K kinase/Akt. Also, in cytomegalovirus-infected cells, this ligand binds the UL16 glycoprotein and is prevented from activating the immune system. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULBP1	NM_025218.4	c.*259G>C		3_prime_UTR_variant	5/5	ENST00000229708.4
ULBP1	NM_001317089.2	c.*259G>C		3_prime_UTR_variant	3/3
ULBP1	XM_017011322.2	c.*226G>C		3_prime_UTR_variant	4/4
ULBP1	NR_133659.2	n.2449G>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULBP1	ENST00000229708.4	c.*259G>C		3_prime_UTR_variant	5/5	1	NM_025218.4	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19050 AN: 151922 Hom.: 2154 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0262 AC: 137 AN: 5236 Hom.: 9 Cov.: 0 AF XY: 0.0257 AC XY: 69 AN XY: 2690

Gnomad4 AFR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0513

GnomAD4 genome AF: 0.126 AC: 19102 AN: 152040 Hom.: 2162 Cov.: 32 AF XY: 0.128 AC XY: 9495 AN XY: 74356

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0400

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0832 Hom.: 147

Bravo AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.85
Dann	Benign	0.27

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: rs1977656; hg19: chr6-150292741;