rs17370826

Variant names:

• chr1-179914071-A-G
• rs17370826
• NM_015602.4:c.964+17A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015602.4(TOR1AIP1):​c.964+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,606,726 control chromosomes in the GnomAD database, including 3,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (311 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3140 hom.)
• Consequence: TOR1AIP1 NM_015602.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.470
• Publications: 3 publications found

Genes affected

TOR1AIP1 (HGNC:29456): (torsin 1A interacting protein 1) This gene encodes a type 2 integral membrane protein that binds A- and B-type lamins. The encoded protein localizes to the inner nuclear membrane and may be involved in maintaining the attachment of the nuclear membrane to the nuclear lamina during cell division. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

TOR1AIP1 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2Y

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-179914071-A-G is Benign according to our data. Variant chr1-179914071-A-G is described in ClinVar as Benign. ClinVar VariationId is 257705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOR1AIP1	NM_015602.4	c.964+17A>G		intron_variant	Intron 9 of 9	ENST00000606911.7	NP_056417.2
TOR1AIP1	NM_001267578.2	c.967+17A>G		intron_variant	Intron 9 of 9		NP_001254507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.964+17A>G		intron_variant	Intron 9 of 9	1	NM_015602.4	ENSP00000476687.1

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7909 AN: 152144 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0526

GnomAD2 exomes AF: 0.0556 AC: 13729 AN: 247136 AF XY: 0.0569

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.00303

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0574

GnomAD4 exome AF: 0.0608 AC: 88501 AN: 1454464 Hom.: 3140 Cov.: 29 AF XY: 0.0607 AC XY: 43948 AN XY: 723654

African (AFR) AF: 0.0123 AC: 407 AN: 33212

American (AMR) AF: 0.0432 AC: 1900 AN: 43978

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 294 AN: 26038

East Asian (EAS) AF: 0.00197 AC: 78 AN: 39578

South Asian (SAS) AF: 0.0464 AC: 3948 AN: 85076

European-Finnish (FIN) AF: 0.134 AC: 7151 AN: 53350

Middle Eastern (MID) AF: 0.0259 AC: 149 AN: 5754

European-Non Finnish (NFE) AF: 0.0644 AC: 71298 AN: 1107350

Other (OTH) AF: 0.0545 AC: 3276 AN: 60128

GnomAD4 genome AF: 0.0519 AC: 7908 AN: 152262 Hom.: 311 Cov.: 32 AF XY: 0.0541 AC XY: 4030 AN XY: 74442

African (AFR) AF: 0.0151 AC: 628 AN: 41562

American (AMR) AF: 0.0564 AC: 862 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5182

South Asian (SAS) AF: 0.0400 AC: 193 AN: 4828

European-Finnish (FIN) AF: 0.135 AC: 1432 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4604 AN: 68012

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0594 Hom.: 62

Bravo AF: 0.0426

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2Y Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17370826; hg19: chr1-179883206;