chr4-73413587-G-C

Position:

• chr4-73413587-G-C

Variant summary

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

The NM_000477.7(ALB):​c.1011G>C​(p.Lys337Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7	c.1011G>C	p.Lys337Asn	missense_variant	8/15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1011G>C	p.Lys337Asn	missense_variant	8/15	1	NM_000477.7	ENSP00000295897	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.;.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.1	M;.;.;.;.
MutationTaster	Benign	0.59	N;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.013	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		0.95	P;P;D;.;D
Vest4		0.52
MutPred		0.46		Loss of methylation at K337 (P = 0.0069);.;.;Loss of methylation at K337 (P = 0.0069);.;
MVP		0.88
MPC		0.40
ClinPred		0.83	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.43
gMVP		0.32

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: rs72552710; hg19: chr4-74279304;