rs1056400

Positions:

• chr5-150402064-T-C

Variant summary

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

The NM_001025159.3(CD74):​c.*176A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,538,994 control chromosomes in the GnomAD database, including 11,109 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 0.083 (697 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10412 hom.)
• Consequence: CD74 NM_001025159.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD74	NM_001025159.3	c.*176A>G		3_prime_UTR_variant	9/9	ENST00000009530.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD74	ENST00000009530.13	c.*176A>G		3_prime_UTR_variant	9/9	2	NM_001025159.3	P1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12688 AN: 152034 Hom.: 698 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0844

GnomAD4 exome AF: 0.116 AC: 160520 AN: 1386842 Hom.: 10412 Cov.: 32 AF XY: 0.114 AC XY: 78152 AN XY: 684306

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.0450

Gnomad4 ASJ exome AF: 0.0578

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.0693

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0833 AC: 12679 AN: 152152 Hom.: 697 Cov.: 32 AF XY: 0.0834 AC XY: 6200 AN XY: 74368

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0840

Alfa AF: 0.103 Hom.: 869

Bravo AF: 0.0795

Asia WGS AF: 0.110 AC: 383 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1056400; hg19: chr5-149781627;