4-73416259-G-C

Position:

• chr4-73416259-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000477.7(ALB):​c.1195G>C​(p.Asp399His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. D399N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ALB NM_000477.7 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.35

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21391872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7	c.1195G>C	p.Asp399His	missense_variant	10/15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1195G>C	p.Asp399His	missense_variant	10/15	1	NM_000477.7	ENSP00000295897.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460412 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Alloalbuminemia Other:1

not provided, no classification provided

literature only

ClinVar Staff, National Center for Biotechnology Information (NCBI)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Uncertain	0.78	D;.;.;.;.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.77	T;T;T;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	M;.;.;.;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	D;.;.;D;N;D;N
REVEL	Uncertain	0.30
Sift	Benign	0.15	T;.;.;D;D;T;T
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D
Polyphen		0.016	B;.;.;B;B;.;B
Vest4		0.21
MutPred		0.39		Gain of methylation at K402 (P = 0.0424);.;.;.;.;Gain of methylation at K402 (P = 0.0424);.;
MVP		0.65
MPC		0.25
ClinPred		0.18	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.35

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: rs77514449; hg19: chr4-74281976;