rs3775486

Positions:

• chr4-73409798-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000477.7(ALB):​c.615+311C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,688 control chromosomes in the GnomAD database, including 14,494 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 0.43 (14494 hom., cov: 31)
• Consequence: ALB NM_000477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALB	NM_000477.7	c.615+311C>A		intron_variant		ENST00000295897.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALB	ENST00000295897.9	c.615+311C>A		intron_variant		1	NM_000477.7	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65519 AN: 151570 Hom.: 14465 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.433 AC: 65615 AN: 151688 Hom.: 14494 Cov.: 31 AF XY: 0.437 AC XY: 32340 AN XY: 74076

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.475

Alfa AF: 0.411 Hom.: 15610

Bravo AF: 0.444

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.9
DANN	Benign	0.85

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: rs3775486; hg19: chr4-74275515;