11-408352-C-A

Variant names:

• chr11-408352-C-A
• rs7396562
• NM_001135054.2:c.207-146G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIGIRR	NM_001135054.2	c.207-146G>T		intron_variant	Intron 3 of 9	ENST00000431843.7	NP_001128526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGIRR	ENST00000431843.7	c.207-146G>T		intron_variant	Intron 3 of 9	1	NM_001135054.2	ENSP00000403104.2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32841 AN: 152014 Hom.: 4109 Cov.: 33

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

African (AFR) AF: 0.261 AC: 5540 AN: 21208

American (AMR) AF: 0.232 AC: 5444 AN: 23448

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 2975 AN: 16930

East Asian (EAS) AF: 0.635 AC: 22107 AN: 34834

South Asian (SAS) AF: 0.330 AC: 19565 AN: 59342

European-Finnish (FIN) AF: 0.145 AC: 4789 AN: 33010

Middle Eastern (MID) AF: 0.229 AC: 675 AN: 2952

European-Non Finnish (NFE) AF: 0.158 AC: 109584 AN: 694556

Other (OTH) AF: 0.210 AC: 8781 AN: 41814

GnomAD4 genome AF: 0.216 AC: 32852 AN: 152132 Hom.: 4100 Cov.: 33 AF XY: 0.220 AC XY: 16352 AN XY: 74400

African (AFR) AF: 0.262 AC: 10881 AN: 41492

American (AMR) AF: 0.231 AC: 3537 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 604 AN: 3454

East Asian (EAS) AF: 0.578 AC: 2978 AN: 5156

South Asian (SAS) AF: 0.355 AC: 1713 AN: 4830

European-Finnish (FIN) AF: 0.133 AC: 1414 AN: 10602

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11027 AN: 67980

Other (OTH) AF: 0.220 AC: 466 AN: 2116

Alfa AF: 0.185 Hom.: 4388

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
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7396562; hg19: chr11-408352;