4-73418969-C-T

Position:

• chr4-73418969-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.1653-538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,086 control chromosomes in the GnomAD database, including 1,907 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 0.14 (1907 hom., cov: 31)
• Consequence: ALB NM_000477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7	c.1653-538C>T		intron_variant		ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1653-538C>T		intron_variant		1	NM_000477.7	ENSP00000295897.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21859 AN: 151968 Hom.: 1906 Cov.: 31

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.144 AC: 21863 AN: 152086 Hom.: 1907 Cov.: 31 AF XY: 0.143 AC XY: 10595 AN XY: 74318

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.137

Alfa AF: 0.177 Hom.: 2189

Bravo AF: 0.134

Asia WGS AF: 0.0890 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.46

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: rs3926327; hg19: chr4-74284686;