rs2748249

Variant names:

• chr5-150413037-C-A
• rs2748249
• NM_001025159.3:c.-288G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150413037-C-A
• chr5-150413037-C-G
• chr5-150413037-C-T

Variant summary

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

The NM_001025159.3(CD74):​c.-288G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,065,770 control chromosomes in the GnomAD database, including 17,227 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 0.14 (1908 hom., cov: 33)
  • Exomes 𝑓: 0.18 (15319 hom.)
• Consequence: CD74 NM_001025159.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 5 publications found

Genes affected

CD74 (HGNC:1697): (CD74 molecule) The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. It also serves as cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF) which, when bound to the encoded protein, initiates survival pathways and cell proliferation. This protein also interacts with amyloid precursor protein (APP) and suppresses the production of amyloid beta (Abeta). Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025159.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD74	NM_001025159.3	MANE Select	c.-288G>T		upstream_gene	N/A	NP_001020330.1	P04233-1
	CD74	NM_004355.4		c.-288G>T		upstream_gene	N/A	NP_004346.1	P04233-2
	CD74	NM_001364083.3		c.-288G>T		upstream_gene	N/A	NP_001351012.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD74	ENST00000009530.13	TSL:2 MANE Select	c.-288G>T		upstream_gene	N/A	ENSP00000009530.7	P04233-1
	CD74	ENST00000517791.1	TSL:3	n.-125G>T		upstream_gene	N/A
	CD74	ENST00000523813.2	TSL:4	n.-68G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21799 AN: 152118 Hom.: 1898 Cov.: 33

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.182 AC: 166343 AN: 913534 Hom.: 15319 AF XY: 0.182 AC XY: 79830 AN XY: 439236

African (AFR) AF: 0.0435 AC: 911 AN: 20962

American (AMR) AF: 0.158 AC: 2107 AN: 13338

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 1965 AN: 13038

East Asian (EAS) AF: 0.120 AC: 2660 AN: 22096

South Asian (SAS) AF: 0.175 AC: 8099 AN: 46406

European-Finnish (FIN) AF: 0.209 AC: 2395 AN: 11472

Middle Eastern (MID) AF: 0.187 AC: 444 AN: 2372

European-Non Finnish (NFE) AF: 0.189 AC: 141400 AN: 746650

Other (OTH) AF: 0.171 AC: 6362 AN: 37200

GnomAD4 genome AF: 0.143 AC: 21827 AN: 152236 Hom.: 1908 Cov.: 33 AF XY: 0.144 AC XY: 10726 AN XY: 74416

African (AFR) AF: 0.0470 AC: 1955 AN: 41562

American (AMR) AF: 0.149 AC: 2280 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.119 AC: 614 AN: 5176

South Asian (SAS) AF: 0.164 AC: 792 AN: 4830

European-Finnish (FIN) AF: 0.218 AC: 2312 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12886 AN: 67980

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.167 Hom.: 3868

Bravo AF: 0.133

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.8
DANN	Benign	0.72
PhyloP100		-0.062
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2748249; hg19: chr5-149792600;