chr4-73420262-A-C

Position:

• chr4-73420262-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000477.7(ALB):​c.1794A>C​(p.Lys598Asn) 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23463237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7	c.1794A>C	p.Lys598Asn	missense_variant	14/15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1794A>C	p.Lys598Asn	missense_variant	14/15	1	NM_000477.7	ENSP00000295897	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Uncertain	0.77	D;.;.;.;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.73	T;T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.;.;.
MutationTaster	Benign	0.71	D;D;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;.;.;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.23	T;.;.;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.012	B;.;.;B;B;B
Vest4		0.40
MutPred		0.36		Loss of ubiquitination at K598 (P = 0.0067);.;.;.;.;.;
MVP		0.88
MPC		0.26
ClinPred		0.11	T
GERP RS		0.26
Varity_R		0.16
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs75738598; hg19: chr4-74285979;