chr4-73404283-T-C

Position:

• chr4-73404283-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000441319.5(ALB):​c.48-86T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,443,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: ALB ENST00000441319.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALB	NM_000477.7			upstream_gene_variant		ENST00000295897.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALB	ENST00000295897.9			upstream_gene_variant		1	NM_000477.7	P1

Frequencies

GnomAD3 genomes AF: 0.000532 AC: 81 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000539 AC: 135 AN: 250544 Hom.: 0 AF XY: 0.000620 AC XY: 84 AN XY: 135392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000732

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000441 AC: 569 AN: 1291440 Hom.: 0 Cov.: 19 AF XY: 0.000462 AC XY: 301 AN XY: 651972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000338

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000484

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000450

Gnomad4 OTH exome AF: 0.000714

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74486

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000682 Hom.: 0

Bravo AF: 0.000506

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperthyroxinemia, dysalbuminemic Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375806262; hg19: chr4-74270000;