dbSNP rs4074794: SIGIRR:c.7+53C>T (chr11-409815-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.887

Publications

17 publications found

Variant links:

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]

SIGIRR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135054.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIGIRR	NM_001135054.2	MANE Select	c.7+53C>T	intron	N/A	NP_001128526.1	Q6IA17-1
SIGIRR	NM_001135053.2		c.7+53C>T	intron	N/A	NP_001128525.1	Q6IA17-1
SIGIRR	NM_021805.3		c.7+53C>T	intron	N/A	NP_068577.2	Q6IA17-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIGIRR	ENST00000431843.7	TSL:1 MANE Select	c.7+53C>T	intron	N/A	ENSP00000403104.2	Q6IA17-1
SIGIRR	ENST00000397632.7	TSL:1	c.7+53C>T	intron	N/A	ENSP00000380756.3	Q6IA17-1
SIGIRR	ENST00000531205.5	TSL:2	c.7+53C>T	intron	N/A	ENSP00000433022.1	C9JFX4

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32892

AN:

152072

Hom.:

4134

Cov.:

show subpopulations

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.:

AF XY:

0.183

AC XY:

107318

AN XY:

587952

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

8673

17346

26018

34691

43364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6416

12832

19248

25664

32080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.216

AC:

32903

AN:

152190

Hom.:

4125

Cov.:

AF XY:

0.220

AC XY:

16372

AN XY:

74420

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11048

AN:

67994

Other (OTH)

AF:

0.221

AC:

466

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1340

2679

4019

5358

6698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.89

PromoterAI

0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over