11-409815-G-C

Variant names:

• chr11-409815-G-C
• rs4074794
• NM_001135054.2:c.7+53C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135054.2(SIGIRR):​c.7+53C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGIRR NM_001135054.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGIRR	NM_001135054.2	c.7+53C>G		intron_variant	Intron 2 of 9	ENST00000431843.7	NP_001128526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGIRR	ENST00000431843.7	c.7+53C>G		intron_variant	Intron 2 of 9	1	NM_001135054.2	ENSP00000403104.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1212714 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 588766

African (AFR) AF: 0.00 AC: 0 AN: 24164

American (AMR) AF: 0.00 AC: 0 AN: 13176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17632

East Asian (EAS) AF: 0.00 AC: 0 AN: 27364

South Asian (SAS) AF: 0.00 AC: 0 AN: 47398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 986770

Other (OTH) AF: 0.00 AC: 0 AN: 48798

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.9
DANN	Benign	0.70
PhyloP100		0.89
PromoterAI		0.030	Neutral

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

Other links and lift over

dbSNP: rs4074794; hg19: chr11-409815;