Genetic Variant CD74:p.Arg10Gln (chr5-150412721-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001025159.3(CD74):c.29G>A(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CD74
NM_001025159.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.197

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04679495).

BP6

Variant 5-150412721-C-T is Benign according to our data. Variant chr5-150412721-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3488176.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025159.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD74	NM_001025159.3	MANE Select	c.29G>A	p.Arg10Gln	missense	Exon 1 of 9	NP_001020330.1	P04233-1
CD74	NM_004355.4		c.29G>A	p.Arg10Gln	missense	Exon 1 of 8	NP_004346.1	P04233-2
CD74	NM_001364083.3		c.29G>A	p.Arg10Gln	missense	Exon 1 of 7	NP_001351012.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD74	ENST00000009530.13	TSL:2 MANE Select	c.29G>A	p.Arg10Gln	missense	Exon 1 of 9	ENSP00000009530.7	P04233-1
CD74	ENST00000353334.11	TSL:1	c.29G>A	p.Arg10Gln	missense	Exon 1 of 8	ENSP00000230685.6	P04233-2
CD74	ENST00000377795.7	TSL:1	c.29G>A	p.Arg10Gln	missense	Exon 1 of 6	ENSP00000367026.3	P04233-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.7

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0057

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.76

M_CAP

Benign

0.0092

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PhyloP100

-0.20

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.20

REVEL

Benign

0.13

Sift

Benign

0.23

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.17

MutPred

0.11

Loss of MoRF binding (P = 0.0298)

MVP

0.28

MPC

0.55

ClinPred

0.14

GERP RS

2.4

PromoterAI

-0.22

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.12

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over