rs79738788

Variant names:

• chr4-73419575-A-C
• rs79738788
• NM_000477.7:c.1721A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-73419575-A-C
• chr4-73419575-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000477.7(ALB):​c.1721A>C​(p.Asp574Ala) 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. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D574G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.16
• Publications: 5 publications found

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]

ALB Gene-Disease associations (from GenCC):

• congenital analbuminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperthyroxinemia, familial dysalbuminemic

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3898211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000477.7. 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
	ALB	NM_000477.7	MANE Select	c.1721A>C	p.Asp574Ala	missense	Exon 13 of 15	NP_000468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALB	ENST00000295897.9	TSL:1 MANE Select	c.1721A>C	p.Asp574Ala	missense	Exon 13 of 15	ENSP00000295897.4
	ALB	ENST00000415165.6	TSL:1	c.1145A>C	p.Asp382Ala	missense	Exon 9 of 11	ENSP00000401820.2
	ALB	ENST00000876051.1		c.1784A>C	p.Asp595Ala	missense	Exon 13 of 15	ENSP00000546110.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Alloalbuminemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.2
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.37
Sift	Benign	0.15	T
Sift4G	Uncertain	0.042	D
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.54		Loss of ubiquitination at K569 (P = 0.0456)
MVP		0.92
MPC		0.26
ClinPred		0.21	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.45
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs79738788; hg19: chr4-74285292;