Genetic Variant ULBP1:c.*259G>C (chr6-149971605-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.495

Publications

3 publications found

Variant links:

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]

ULBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
ULBP1	NM_025218.4 link	c.*259G>C	3_prime_UTR_variant	Exon 5 of 5	ENST00000229708.4	NP_079494.1	Q9BZM6
ULBP1	NR_133659.2 link	n.2449G>C	non_coding_transcript_exon_variant	Exon 5 of 5
ULBP1	NM_001317089.2 link	c.*259G>C	3_prime_UTR_variant	Exon 3 of 3		NP_001304018.1	Q9BZM6
ULBP1	XM_017011322.2 link	c.*226G>C	3_prime_UTR_variant	Exon 4 of 4		XP_016866811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULBP1	ENST00000229708.4 link	c.*259G>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_025218.4	ENSP00000229708.2		Q9BZM6

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19050

AN:

151922

Hom.:

2154

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0257

AC XY:

AN XY:

2690

show subpopulations

African (AFR)

AF:

0.152

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.417

AC:

AN:

South Asian (SAS)

AF:

0.105

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0213

AC:

104

AN:

4874

Other (OTH)

AF:

0.0513

AC:

AN:

156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19102

AN:

152040

Hom.:

2162

Cov.:

AF XY:

0.128

AC XY:

9495

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.277

AC:

11488

AN:

41418

American (AMR)

AF:

0.129

AC:

1968

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3464

East Asian (EAS)

AF:

0.357

AC:

1840

AN:

5148

South Asian (SAS)

AF:

0.152

AC:

732

AN:

4820

European-Finnish (FIN)

AF:

0.0400

AC:

424

AN:

10596

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0331

AC:

2252

AN:

68000

Other (OTH)

AF:

0.127

AC:

267

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

659

1318

1977

2636

3295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.27

PhyloP100

-0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over