11-408352-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135054.2(SIGIRR):​c.207-146G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,080,226 control chromosomes in the GnomAD database, including 26,750 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 0.22 ( 4100 hom., cov: 33)
Exomes 𝑓: 0.19 ( 22650 hom. )

Consequence

SIGIRR
NM_001135054.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269
Variant links:
Genes affected
SIGIRR (HGNC:30575): (single Ig and TIR domain containing) Predicted to enable NAD+ nucleosidase activity. Involved in negative regulation of DNA-binding transcription factor activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SIGIRRNM_001135054.2 linkuse as main transcriptc.207-146G>T intron_variant ENST00000431843.7 NP_001128526.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIGIRRENST00000431843.7 linkuse as main transcriptc.207-146G>T intron_variant 1 NM_001135054.2 ENSP00000403104 P1Q6IA17-1

Frequencies

GnomAD3 genomes
AF:
0.216
AC:
32841
AN:
152014
Hom.:
4109
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.262
Gnomad AMI
AF:
0.182
Gnomad AMR
AF:
0.231
Gnomad ASJ
AF:
0.175
Gnomad EAS
AF:
0.578
Gnomad SAS
AF:
0.357
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.222
GnomAD4 exome
AF:
0.193
AC:
179460
AN:
928094
Hom.:
22650
AF XY:
0.198
AC XY:
92489
AN XY:
467544
show subpopulations
Gnomad4 AFR exome
AF:
0.261
Gnomad4 AMR exome
AF:
0.232
Gnomad4 ASJ exome
AF:
0.176
Gnomad4 EAS exome
AF:
0.635
Gnomad4 SAS exome
AF:
0.330
Gnomad4 FIN exome
AF:
0.145
Gnomad4 NFE exome
AF:
0.158
Gnomad4 OTH exome
AF:
0.210
GnomAD4 genome
AF:
0.216
AC:
32852
AN:
152132
Hom.:
4100
Cov.:
33
AF XY:
0.220
AC XY:
16352
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.262
Gnomad4 AMR
AF:
0.231
Gnomad4 ASJ
AF:
0.175
Gnomad4 EAS
AF:
0.578
Gnomad4 SAS
AF:
0.355
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.220
Alfa
AF:
0.174
Hom.:
2240
Bravo
AF:
0.224
Asia WGS
AF:
0.454
AC:
1578
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
15
DANN
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs7396562; hg19: chr11-408352; API