dbSNP rs1056400: CD74:c.*176A>G (chr5-150402064-T-C) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

Publications

15 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:

Genome browser will be placed here

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=-0.91).

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 rank	MANE	Protein	UniProt
CD74	NM_001025159.3 link	c.*176A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000009530.13	NP_001020330.1	P04233-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD74	ENST00000009530.13 link	c.*176A>G		3_prime_UTR_variant	Exon 9 of 9	2	NM_001025159.3	ENSP00000009530.7		P04233-1

Frequencies

GnomAD3 genomes

AF:

0.0835

AC:

12688

AN:

152034

Hom.:

698

Cov.:

show subpopulations

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.:

AF XY:

0.114

AC XY:

78152

AN XY:

684306

show subpopulations

African (AFR)

AF:

0.0200

AC:

632

AN:

31596

American (AMR)

AF:

0.0450

AC:

1607

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.0578

AC:

1454

AN:

25166

East Asian (EAS)

AF:

0.283

AC:

10110

AN:

35734

South Asian (SAS)

AF:

0.0693

AC:

5489

AN:

79228

European-Finnish (FIN)

AF:

0.100

AC:

3722

AN:

37130

Middle Eastern (MID)

AF:

0.0718

AC:

409

AN:

5696

European-Non Finnish (NFE)

AF:

0.121

AC:

130987

AN:

1078658

Other (OTH)

AF:

0.105

AC:

6110

AN:

57942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7392

14783

22175

29566

36958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4864

9728

14592

19456

24320

<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:

0.0833

AC:

12679

AN:

152152

Hom.:

697

Cov.:

AF XY:

0.0834

AC XY:

6200

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0235

AC:

976

AN:

41534

American (AMR)

AF:

0.0584

AC:

893

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3468

East Asian (EAS)

AF:

0.238

AC:

1231

AN:

5162

South Asian (SAS)

AF:

0.0728

AC:

350

AN:

4808

European-Finnish (FIN)

AF:

0.101

AC:

1071

AN:

10582

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7652

AN:

67986

Other (OTH)

AF:

0.0840

AC:

177

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

592

1184

1776

2368

2960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.101

Hom.:

1241

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

(source)

DANN

Benign

0.58

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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