rs3775486

Variant names:

• chr4-73409798-C-A
• rs3775486
• NM_000477.7:c.615+311C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALB	NM_000477.7	MANE Select	c.615+311C>A		intron	N/A	NP_000468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALB	ENST00000295897.9	TSL:1 MANE Select	c.615+311C>A		intron	N/A	ENSP00000295897.4
	ALB	ENST00000415165.6	TSL:1	c.138-2198C>A		intron	N/A	ENSP00000401820.2
	ALB	ENST00000509063.5	TSL:5	c.615+311C>A		intron	N/A	ENSP00000422784.1

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

African (AFR) AF: 0.455 AC: 18814 AN: 41356

American (AMR) AF: 0.535 AC: 8155 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2297 AN: 5144

South Asian (SAS) AF: 0.431 AC: 2072 AN: 4810

European-Finnish (FIN) AF: 0.423 AC: 4428 AN: 10470

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

European-Non Finnish (NFE) AF: 0.391 AC: 26555 AN: 67878

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.412 Hom.: 18696

Bravo AF: 0.444

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		-0.70
PromoterAI		-0.0029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3775486; hg19: chr4-74275515;