1-179882051-C-G

Position:

• chr1-179882051-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000610272.1(ENSG00000272906):​n.545G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 160,906 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (145 hom., cov: 31)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: ENST00000610272.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

Genes affected

(HGNC:):

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=-0.95).
• BP6: Variant 1-179882051-C-G is Benign according to our data. Variant chr1-179882051-C-G is described in ClinVar as [Benign]. Clinvar id is 1297864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000610272.1	n.545G>C		non_coding_transcript_exon_variant	1/1
TOR1AIP1	ENST00000528443.6	c.-452C>G		5_prime_UTR_variant	1/10	2		A2

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4101 AN: 152050 Hom.: 144 Cov.: 31

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0109 AC: 95 AN: 8738 Hom.: 0 Cov.: 0 AF XY: 0.0113 AC XY: 49 AN XY: 4318

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00643

Gnomad4 OTH exome AF: 0.0184

GnomAD4 genome AF: 0.0270 AC: 4106 AN: 152168 Hom.: 145 Cov.: 31 AF XY: 0.0268 AC XY: 1992 AN XY: 74384

Gnomad4 AFR AF: 0.0764

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.00701

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00545 Hom.: 4

Bravo AF: 0.0301

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs112714304; hg19: chr1-179851186;