4-73425201-C-T

Variant names:

• chr4-73425201-C-T
• rs28585480
• ENST00000876006.1:c.*24-949C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000876006.1(ALB):​c.*24-949C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,892 control chromosomes in the GnomAD database, including 15,850 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15850 hom., cov: 32)
• Consequence: ALB ENST00000876006.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 2 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• hyperthyroxinemia, familial dysalbuminemic

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876006.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALB	ENST00000876006.1		c.*24-949C>T		intron	N/A	ENSP00000546065.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68647 AN: 151774 Hom.: 15820 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.453 AC: 68735 AN: 151892 Hom.: 15850 Cov.: 32 AF XY: 0.457 AC XY: 33945 AN XY: 74236

African (AFR) AF: 0.461 AC: 19118 AN: 41426

American (AMR) AF: 0.545 AC: 8325 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1931 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2291 AN: 5140

South Asian (SAS) AF: 0.480 AC: 2309 AN: 4812

European-Finnish (FIN) AF: 0.455 AC: 4794 AN: 10544

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28401 AN: 67924

Other (OTH) AF: 0.490 AC: 1033 AN: 2110

Alfa AF: 0.322 Hom.: 940

Bravo AF: 0.460

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.076
DANN	Benign	0.46
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28585480; hg19: chr4-74290918;