11-408352-C-T

Variant names:

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

Variant summary

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

The NM_021805.3(SIGIRR):​c.207-146G>A 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SIGIRR NM_021805.3 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: 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=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGIRR	NM_001135054.2	MANE Select	c.207-146G>A		intron	N/A	NP_001128526.1
	SIGIRR	NM_001135053.2		c.207-146G>A		intron	N/A	NP_001128525.1
	SIGIRR	NM_021805.3		c.207-146G>A		intron	N/A	NP_068577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGIRR	ENST00000431843.7	TSL:1 MANE Select	c.207-146G>A		intron	N/A	ENSP00000403104.2
	SIGIRR	ENST00000397632.7	TSL:1	c.207-146G>A		intron	N/A	ENSP00000380756.3
	SIGIRR	ENST00000531205.5	TSL:2	c.207-146G>A		intron	N/A	ENSP00000433022.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 929308 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 468138

African (AFR) AF: 0.00 AC: 0 AN: 21244

American (AMR) AF: 0.00 AC: 0 AN: 23472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16942

East Asian (EAS) AF: 0.00 AC: 0 AN: 34874

South Asian (SAS) AF: 0.00 AC: 0 AN: 59406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2960

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 695526

Other (OTH) AF: 0.00 AC: 0 AN: 41862

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		-0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;