rs4074794

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-409815-G-A
• chr11-409815-G-C
• chr11-409815-G-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.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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIGIRR	NM_001135054.2	c.7+53C>T		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>T		intron_variant	Intron 2 of 9	1	NM_001135054.2	ENSP00000403104.2

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

African (AFR) AF: 0.261 AC: 6300 AN: 24142

American (AMR) AF: 0.203 AC: 2664 AN: 13122

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 2953 AN: 17612

East Asian (EAS) AF: 0.648 AC: 17719 AN: 27354

South Asian (SAS) AF: 0.299 AC: 14049 AN: 47020

European-Finnish (FIN) AF: 0.138 AC: 5869 AN: 42390

Middle Eastern (MID) AF: 0.227 AC: 1126 AN: 4952

European-Non Finnish (NFE) AF: 0.160 AC: 158219 AN: 986000

Other (OTH) AF: 0.211 AC: 10283 AN: 48740

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

African (AFR) AF: 0.263 AC: 10898 AN: 41514

American (AMR) AF: 0.231 AC: 3542 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2985 AN: 5154

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

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10614

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

European-Non Finnish (NFE) AF: 0.162 AC: 11048 AN: 67994

Other (OTH) AF: 0.221 AC: 466 AN: 2112

Alfa AF: 0.185 Hom.: 1589

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
PhyloP100		0.89
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV58990125; COSMIC: COSV58990125;