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GeneBe

3-186613180-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001622.4(AHSG):c.39C>G(p.Leu13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,722 control chromosomes in the GnomAD database, including 21,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3506 hom., cov: 31)
Exomes 𝑓: 0.15 ( 17803 hom. )

Consequence

AHSG
NM_001622.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.124
Variant links:
Genes affected
AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]
HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-186613180-C-G is Benign according to our data. Variant chr3-186613180-C-G is described in ClinVar as [Benign]. Clinvar id is 3058930.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.124 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AHSGNM_001622.4 linkuse as main transcriptc.39C>G p.Leu13= synonymous_variant 1/7 ENST00000411641.7
AHSGNM_001354571.2 linkuse as main transcriptc.39C>G p.Leu13= synonymous_variant 1/7
AHSGNM_001354572.2 linkuse as main transcriptc.39C>G p.Leu13= synonymous_variant 1/7
AHSGNM_001354573.2 linkuse as main transcriptc.39C>G p.Leu13= synonymous_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHSGENST00000411641.7 linkuse as main transcriptc.39C>G p.Leu13= synonymous_variant 1/71 NM_001622.4 P3
HRG-AS1ENST00000630178.2 linkuse as main transcriptn.239-33214G>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.194
AC:
29543
AN:
151920
Hom.:
3500
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.331
Gnomad AMI
AF:
0.0581
Gnomad AMR
AF:
0.174
Gnomad ASJ
AF:
0.247
Gnomad EAS
AF:
0.122
Gnomad SAS
AF:
0.194
Gnomad FIN
AF:
0.0958
Gnomad MID
AF:
0.264
Gnomad NFE
AF:
0.136
Gnomad OTH
AF:
0.216
GnomAD3 exomes
AF:
0.158
AC:
39644
AN:
251210
Hom.:
3701
AF XY:
0.158
AC XY:
21416
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.336
Gnomad AMR exome
AF:
0.127
Gnomad ASJ exome
AF:
0.241
Gnomad EAS exome
AF:
0.113
Gnomad SAS exome
AF:
0.212
Gnomad FIN exome
AF:
0.0955
Gnomad NFE exome
AF:
0.139
Gnomad OTH exome
AF:
0.159
GnomAD4 exome
AF:
0.149
AC:
218115
AN:
1461684
Hom.:
17803
Cov.:
33
AF XY:
0.150
AC XY:
109076
AN XY:
727162
show subpopulations
Gnomad4 AFR exome
AF:
0.340
Gnomad4 AMR exome
AF:
0.133
Gnomad4 ASJ exome
AF:
0.240
Gnomad4 EAS exome
AF:
0.144
Gnomad4 SAS exome
AF:
0.208
Gnomad4 FIN exome
AF:
0.0922
Gnomad4 NFE exome
AF:
0.139
Gnomad4 OTH exome
AF:
0.163
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.194
AC:
29560
AN:
152038
Hom.:
3506
Cov.:
31
AF XY:
0.191
AC XY:
14177
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.330
Gnomad4 AMR
AF:
0.174
Gnomad4 ASJ
AF:
0.247
Gnomad4 EAS
AF:
0.122
Gnomad4 SAS
AF:
0.194
Gnomad4 FIN
AF:
0.0958
Gnomad4 NFE
AF:
0.136
Gnomad4 OTH
AF:
0.215
Alfa
AF:
0.163
Hom.:
775
Bravo
AF:
0.206
Asia WGS
AF:
0.167
AC:
580
AN:
3478
EpiCase
AF:
0.146
EpiControl
AF:
0.157

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

AHSG-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 29, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
9.9
Dann
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

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

Other links and lift over

dbSNP: rs4831; hg19: chr3-186330969; COSMIC: COSV56607297; API