rs7396562

Positions:

• chr11-408352-C-A
• chr11-408352-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

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	UniProt
SIGIRR	NM_001135054.2	c.207-146G>T		intron_variant		ENST00000431843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGIRR	ENST00000431843.7	c.207-146G>T		intron_variant		1	NM_001135054.2	P1

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

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

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

Other links and lift over

dbSNP: rs7396562; hg19: chr11-408352;