rs4074794

chr11-409815-G-Achr11-409815-G-Cchr11-409815-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135054.2(SIGIRR):c.7+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,363,522 control chromosomes in the GnomAD database, including 28,365 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 (4125 hom., cov: 34)
  • Exomes 𝑓: 0.18 (24240 hom.)
• Consequence: SIGIRR NM_001135054.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887

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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGIRR	NM_001135054.2	c.7+53C>T		intron_variant		ENST00000431843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGIRR	ENST00000431843.7	c.7+53C>T		intron_variant		1	NM_001135054.2	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32892 AN: 152072 Hom.: 4134 Cov.: 34

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.181 AC: 219182 AN: 1211332 Hom.: 24240 Cov.: 28 AF XY: 0.183 AC XY: 107318 AN XY: 587952

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.648

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.216 AC: 32903 AN: 152190 Hom.: 4125 Cov.: 34 AF XY: 0.220 AC XY: 16372 AN XY: 74420

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.221

Alfa AF: 0.185 Hom.: 1460

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	-0.63
Cadd	Benign	12
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs4074794; hg19: chr11-409815; COSMIC: COSV58990125; COSMIC: COSV58990125;