rs17370826

chr1-179914071-A-G

Variant summary

Our verdict is Benign. Variant got -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:4
• Conservation: PhyloP100: 0.470

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 257705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179914071-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
TOR1AIP1	NM_015602.4	c.964+17A>G		intron_variant		ENST00000606911.7
TOR1AIP1	NM_001267578.2	c.967+17A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOR1AIP1	ENST00000606911.7	c.964+17A>G		intron_variant		1	NM_015602.4	P4

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

GnomAD3 exomes AF: 0.0556 AC: 13729 AN: 247136 Hom.: 523 AF XY: 0.0569 AC XY: 7593 AN XY: 133546

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 SAS exome AF: 0.0468

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

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0432

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.00197

Gnomad4 SAS exome AF: 0.0464

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0644

Gnomad4 OTH exome AF: 0.0545

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

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0516

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.5
Dann	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs17370826; hg19: chr1-179883206;