NM_000477.7:c.1059-487C>T

Variant names:

• chr4-73414548-C-T
• rs667
• NM_000477.7:c.1059-487C>T

Variant summary

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

The NM_000477.7(ALB):​c.1059-487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,998 control chromosomes in the GnomAD database, including 5,018 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 0.25 (5018 hom., cov: 31)
• Consequence: ALB NM_000477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALB	NM_000477.7	c.1059-487C>T		intron_variant	Intron 8 of 14	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1059-487C>T		intron_variant	Intron 8 of 14	1	NM_000477.7	ENSP00000295897.4

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38105 AN: 151880 Hom.: 5007 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.251 AC: 38156 AN: 151998 Hom.: 5018 Cov.: 31 AF XY: 0.253 AC XY: 18807 AN XY: 74300

African (AFR) AF: 0.236 AC: 9790 AN: 41452

American (AMR) AF: 0.359 AC: 5486 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1691 AN: 5142

South Asian (SAS) AF: 0.242 AC: 1162 AN: 4810

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15747 AN: 67946

Other (OTH) AF: 0.286 AC: 604 AN: 2114

Alfa AF: 0.240 Hom.: 553

Bravo AF: 0.261

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.31
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs667; hg19: chr4-74280265;