Genetic Variant CD74:c.-288G>T (chr5-150413037-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0620

Publications

5 publications found

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 was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD74	NM_001025159.3 link	c.-288G>T		upstream_gene_variant		ENST00000009530.13	NP_001020330.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
CD74	ENST00000009530.13 link	c.-288G>T	upstream_gene_variant	2	NM_001025159.3	ENSP00000009530.7
CD74	ENST00000517791.1 link	n.-125G>T	upstream_gene_variant	3
CD74	ENST00000523813.2 link	n.-68G>T	upstream_gene_variant	4
CD74	ENST00000524315.6 link	n.-68G>T	upstream_gene_variant	5

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21799

AN:

152118

Hom.:

1898

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

6394

12789

19183

25578

31972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5546

11092

16638

22184

27730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.143

AC:

21827

AN:

152236

Hom.:

1908

Cov.:

AF XY:

0.144

AC XY:

10726

AN XY:

74416

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12886

AN:

67980

Other (OTH)

AF:

0.144

AC:

305

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

952

1905

2857

3810

4762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.8

(source)

DANN

Benign

0.72

PhyloP100

-0.062

PromoterAI

-0.024

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over