5-150404685-G-C

Variant names:

• chr5-150404685-G-C
• rs750969748
• NM_001025159.3:c.620C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025159.3(CD74):​c.620C>G​(p.Pro207Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P207L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD74 NM_001025159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11239916).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD74	NM_001025159.3	MANE Select	c.620C>G	p.Pro207Arg	missense	Exon 6 of 9	NP_001020330.1	P04233-1
	CD74	NM_004355.4		c.620C>G	p.Pro207Arg	missense	Exon 6 of 8	NP_004346.1	P04233-2
	CD74	NM_001364083.3		c.557C>G	p.Pro186Arg	missense	Exon 5 of 7	NP_001351012.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD74	ENST00000009530.13	TSL:2 MANE Select	c.620C>G	p.Pro207Arg	missense	Exon 6 of 9	ENSP00000009530.7	P04233-1
	CD74	ENST00000353334.11	TSL:1	c.620C>G	p.Pro207Arg	missense	Exon 6 of 8	ENSP00000230685.6	P04233-2
	CD74	ENST00000377795.7	TSL:1	c.441+1574C>G		intron	N/A	ENSP00000367026.3	P04233-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1418258 Hom.: 0 Cov.: 29 AF XY: 0.00000285 AC XY: 2 AN XY: 702094

African (AFR) AF: 0.00 AC: 0 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 38706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25464

East Asian (EAS) AF: 0.00 AC: 0 AN: 37790

South Asian (SAS) AF: 0.00 AC: 0 AN: 80690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1087588

Other (OTH) AF: 0.00 AC: 0 AN: 58866

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.12
Sift	Uncertain	0.010	D
Sift4G	Benign	0.090	T
Polyphen		0.65	P
Vest4		0.093
MutPred		0.45		Loss of catalytic residue at P206 (P = 0.016)
MVP		0.68
MPC		0.71
ClinPred		0.58	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.085
gMVP		0.42
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs750969748; hg19: chr5-149784248;