rs76242087

Variant names:

• chr4-73413589-A-G
• rs76242087
• NM_000477.7:c.1013A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-73413589-A-G
• chr4-73413589-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000477.7(ALB):​c.1013A>G​(p.Asp338Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D338V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.40
• Publications: 3 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

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.1013A>G	p.Asp338Gly	missense	Exon 8 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.1013A>G	p.Asp338Gly	missense	Exon 8 of 15	ENSP00000295897.4
	ALB	ENST00000415165.6	TSL:1	c.437A>G	p.Asp146Gly	missense	Exon 4 of 11	ENSP00000401820.2
	ALB	ENST00000876051.1		c.1076A>G	p.Asp359Gly	missense	Exon 8 of 15	ENSP00000546110.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.21
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.4
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.56
Sift	Benign	0.17	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.0010	B
Vest4		0.63
MutPred		0.81		Gain of catalytic residue at V339 (P = 0.1072)
MVP		0.93
MPC		0.32
ClinPred		0.50	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.43
Mutation Taster		=5/95	disease causing

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

Other links and lift over

dbSNP: rs76242087; hg19: chr4-74279306;