4-73414548-C-T

Position:

• chr4-73414548-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
ALB	NM_000477.7	c.1059-487C>T		intron_variant		ENST00000295897.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALB	ENST00000295897.9	c.1059-487C>T		intron_variant		1	NM_000477.7	P1

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.286

Alfa AF: 0.240 Hom.: 530

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

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: rs667; hg19: chr4-74280265;