5-150402253-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001025159.3(CD74):c.881-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,593,002 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (18 hom.)
• Consequence: CD74 NM_001025159.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001006
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.486

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-150402253-G-A is Benign according to our data. Variant chr5-150402253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD74	NM_001025159.3	c.881-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000009530.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD74	ENST00000009530.13	c.881-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001025159.3	P1

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 358 AN: 152124 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00248 AC: 553 AN: 223172 Hom.: 1 AF XY: 0.00248 AC XY: 299 AN XY: 120700

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00430

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000396

Gnomad FIN exome AF: 0.00323

Gnomad NFE exome AF: 0.00378

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00302 AC: 4357 AN: 1440760 Hom.: 18 Cov.: 30 AF XY: 0.00297 AC XY: 2129 AN XY: 715800

Gnomad4 AFR exome AF: 0.000452

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.00458

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000561

Gnomad4 FIN exome AF: 0.00319

Gnomad4 NFE exome AF: 0.00337

Gnomad4 OTH exome AF: 0.00344

GnomAD4 genome AF: 0.00235 AC: 358 AN: 152242 Hom.: 3 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74438

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.00385

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00349 Hom.: 2

Bravo AF: 0.00194

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CD74: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.57
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0010
dbscSNV1_RF	Benign	0.068
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

LitVar

Other links and lift over

dbSNP: rs142001873; hg19: chr5-149781816;