4-73418166-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000477.7(ALB):c.1507G>C(p.Glu503Gln) 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. 15/21 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. E503K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

Genes affected

ALB (HGNC:399): (albumin) This gene encodes the most abundant protein in human blood. This protein functions in the regulation of blood plasma colloid osmotic pressure and acts as a carrier protein for a wide range of endogenous molecules including hormones, fatty acids, and metabolites, as well as exogenous drugs. Additionally, this protein exhibits an esterase-like activity with broad substrate specificity. The encoded preproprotein is proteolytically processed to generate the mature protein. A peptide derived from this protein, EPI-X4, is an endogenous inhibitor of the CXCR4 chemokine receptor. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29930675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALB	NM_000477.7	c.1507G>C	p.Glu503Gln	missense_variant	12/15	ENST00000295897.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALB	ENST00000295897.9	c.1507G>C	p.Glu503Gln	missense_variant	12/15	1	NM_000477.7	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0099	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.25	T;.;.;.;.;.;T
Eigen	Benign	-0.0055
Eigen_PC	Benign	-0.027
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;.;.;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.19	T;.;.;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T;T;T
Polyphen		0.11	B;.;.;B;P;.;P
Vest4		0.24
MutPred		0.39		Loss of ubiquitination at K499 (P = 0.0381);.;.;.;.;Loss of ubiquitination at K499 (P = 0.0381);.;
MVP		0.80
MPC		0.23
ClinPred		0.65	D
GERP RS		5.1
Varity_R		0.36
gMVP		0.38

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: chr4-74283883;