Variant 4-73404406-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000477.7(ALB):c.79C>A(p.His27Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H27Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALB
NM_000477.7 missense, splice_region

Scores

Splicing: ADA: 0.00006668

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.229

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33260322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALB	NM_000477.7 linkuse as main transcript	c.79C>A	p.His27Asn	missense_variant, splice_region_variant	1/15	ENST00000295897.9	NP_000468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALB	ENST00000295897.9 linkuse as main transcript	c.79C>A	p.His27Asn	missense_variant, splice_region_variant	1/15	1	NM_000477.7	ENSP00000295897	P1	P02768-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456300

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725002

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.068

T;D;.;.;.;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.016

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.53

T;T;T;T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.33

T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.9

.;M;.;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.4

D;D;.;.;N;D;N

REVEL

Benign

0.16

Sift

Benign

0.11

T;T;.;.;T;T;D

Sift4G

Uncertain

0.034

D;D;D;D;T;D;T

Polyphen

0.38, 0.0020, 0.97

.;B;.;.;B;.;D

Vest4

0.36, 0.42, 0.41, 0.40, 0.37, 0.47

MutPred

0.29

.;Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);Loss of stability (P = 0.0297);

MVP

0.87

MPC

0.26

ClinPred

0.70

GERP RS

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.38

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.042

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over