chr15-66386581-A-C

Variant names:

• chr15-66386581-A-C
• rs11071888
• ENST00000570251.1:c.-170T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001398281.1(TIPIN):​c.-9+69T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 165,380 control chromosomes in the GnomAD database, including 3,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3303 hom., cov: 33)
  • Exomes 𝑓: 0.23 (458 hom.)
• Consequence: TIPIN NM_001398281.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253

Genes affected

TIPIN (HGNC:30750): (TIMELESS interacting protein) The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-66386581-A-C is Benign according to our data. Variant chr15-66386581-A-C is described in ClinVar as [Benign]. Clinvar id is 561817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPIN	NM_001398281.1	c.-9+69T>G		intron_variant	Intron 1 of 7		NP_001385210.1
TIPIN	NM_001398283.1	c.-9+26T>G		intron_variant	Intron 1 of 7		NP_001385212.1
TIPIN	NM_001398285.1	c.-236+69T>G		intron_variant	Intron 1 of 6		NP_001385214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPIN	ENST00000570251.1	c.-170T>G		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000458117.1
TIPIN	ENST00000562124.5	c.-9+26T>G		intron_variant	Intron 1 of 7	5		ENSP00000457406.1
TIPIN	ENST00000568216.5	c.-9+69T>G		intron_variant	Intron 1 of 4	3		ENSP00000457172.1
TIPIN	ENST00000561773.1	n.58+69T>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31086 AN: 151934 Hom.: 3299 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.234 AC: 3116 AN: 13332 Hom.: 458 Cov.: 0 AF XY: 0.231 AC XY: 1454 AN XY: 6294

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.205 AC: 31108 AN: 152048 Hom.: 3303 Cov.: 33 AF XY: 0.206 AC XY: 15295 AN XY: 74336

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.213

Alfa AF: 0.180 Hom.: 2448

Bravo AF: 0.210

Asia WGS AF: 0.268 AC: 927 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11071888; hg19: chr15-66678919;