chr5-150406936-C-A

Variant names:

• chr5-150406936-C-A
• NM_001025159.3:c.323G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001025159.3(CD74):​c.323G>T​(p.Arg108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,732 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD74 NM_001025159.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD74	NM_001025159.3	c.323G>T	p.Arg108Leu	missense_variant	Exon 3 of 9	ENST00000009530.13	NP_001020330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD74	ENST00000009530.13	c.323G>T	p.Arg108Leu	missense_variant	Exon 3 of 9	2	NM_001025159.3	ENSP00000009530.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403732 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 694692

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000131

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T;D
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.6	M;M;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.64
MutPred		0.62		Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);
MVP		0.74
MPC		1.5
ClinPred		0.97	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.66
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149786499;