rs2297136

Variant names:

• chr9-5467955-G-A
• rs2297136
• NM_014143.4:c.*93G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-5467955-G-A
• chr9-5467955-G-T

Variant summary

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

The NM_014143.4(CD274):​c.*93G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,092,952 control chromosomes in the GnomAD database, including 165,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24547 hom., cov: 30)
  • Exomes 𝑓: 0.54 (141140 hom.)
• Consequence: CD274 NM_014143.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.710
• Publications: 53 publications found

Genes affected

CD274 (HGNC:17635): (CD274 molecule) This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CD274 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000286162 (HGNC:56906):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-5467955-G-A is Benign according to our data. Variant chr9-5467955-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD274	NM_014143.4	c.*93G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000381577.4	NP_054862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4	c.*93G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_014143.4	ENSP00000370989.3
CD274	ENST00000381573.8	c.*93G>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000370985.4
ENSG00000286162	ENST00000661858.1	n.277-8768C>T		intron_variant	Intron 2 of 2
CD274	ENST00000498261.1	n.*89G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85540 AN: 151754 Hom.: 24528 Cov.: 30

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.540 AC: 508465 AN: 941080 Hom.: 141140 Cov.: 12 AF XY: 0.542 AC XY: 265139 AN XY: 489406

African (AFR) AF: 0.615 AC: 14328 AN: 23294

American (AMR) AF: 0.712 AC: 30475 AN: 42830

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 13397 AN: 22804

East Asian (EAS) AF: 0.799 AC: 29676 AN: 37128

South Asian (SAS) AF: 0.593 AC: 44520 AN: 75136

European-Finnish (FIN) AF: 0.427 AC: 22587 AN: 52888

Middle Eastern (MID) AF: 0.598 AC: 2853 AN: 4768

European-Non Finnish (NFE) AF: 0.511 AC: 326708 AN: 638964

Other (OTH) AF: 0.553 AC: 23921 AN: 43268

GnomAD4 genome AF: 0.564 AC: 85604 AN: 151872 Hom.: 24547 Cov.: 30 AF XY: 0.565 AC XY: 41912 AN XY: 74208

African (AFR) AF: 0.619 AC: 25600 AN: 41382

American (AMR) AF: 0.648 AC: 9883 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2009 AN: 3464

East Asian (EAS) AF: 0.804 AC: 4145 AN: 5154

South Asian (SAS) AF: 0.625 AC: 3008 AN: 4812

European-Finnish (FIN) AF: 0.424 AC: 4464 AN: 10532

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34582 AN: 67972

Other (OTH) AF: 0.583 AC: 1226 AN: 2104

Alfa AF: 0.539 Hom.: 34064

Bravo AF: 0.585

Asia WGS AF: 0.700 AC: 2436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28677815) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.71
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2297136; hg19: chr9-5467955; COSMIC: COSV67501259; COSMIC: COSV67501259;