Variant 5-150402253-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Variant links:

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]

CD74 links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD74	NM_001025159.3 linkuse as main transcript	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 linkuse as main transcript	c.881-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_001025159.3	P1	P04233-1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152124

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00248

AC XY:

299

AN XY:

120700

show subpopulations

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.:

Cov.:

AF XY:

0.00297

AC XY:

2129

AN XY:

715800

show subpopulations

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.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74438

show subpopulations

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.:

Bravo

AF:

0.00194

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over