4-73418969-C-T

Variant names:

• chr4-73418969-C-T
• rs3926327
• NM_000477.7:c.1653-538C>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.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
• Publications: 1 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=-0.83).
• 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 rank	MANE	Protein	UniProt
ALB	NM_000477.7	c.1653-538C>T		intron_variant	Intron 12 of 14	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9	c.1653-538C>T		intron_variant	Intron 12 of 14	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

African (AFR) AF: 0.0705 AC: 2928 AN: 41516

American (AMR) AF: 0.107 AC: 1628 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.130 AC: 671 AN: 5156

South Asian (SAS) AF: 0.0971 AC: 468 AN: 4818

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10564

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13283 AN: 67970

Other (OTH) AF: 0.137 AC: 289 AN: 2116

Alfa AF: 0.176 Hom.: 2615

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
PhyloP100		0.079
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: rs3926327; hg19: chr4-74284686;