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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025218.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ULBP1	NM_025218.4	MANE Select	c.*259G>C	3_prime_UTR	Exon 5 of 5	NP_079494.1	Q9BZM6
ULBP1	NM_001317089.2		c.*259G>C	3_prime_UTR	Exon 3 of 3	NP_001304018.1
ULBP1	NR_133659.2		n.2449G>C	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULBP1	ENST00000229708.4	TSL:1 MANE Select	c.*259G>C		3_prime_UTR	Exon 5 of 5	ENSP00000229708.2	Q9BZM6
	ULBP1	ENST00000954265.1		c.*259G>C		3_prime_UTR	Exon 5 of 5	ENSP00000624324.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over