rs8031897

Variant names:

• chr15-66353753-A-G
• rs8031897
• NM_017858.3:c.-8-798T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017858.3(TIPIN):​c.-8-798T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,046 control chromosomes in the GnomAD database, including 5,622 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 0.26 (5622 hom., cov: 31)
• Consequence: TIPIN NM_017858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPIN	NM_017858.3	c.-8-798T>C		intron_variant	Intron 1 of 7	ENST00000261881.9	NP_060328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPIN	ENST00000261881.9	c.-8-798T>C		intron_variant	Intron 1 of 7	1	NM_017858.3	ENSP00000261881.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38849 AN: 151928 Hom.: 5616 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38876 AN: 152046 Hom.: 5622 Cov.: 31 AF XY: 0.258 AC XY: 19142 AN XY: 74318

African (AFR) AF: 0.128 AC: 5311 AN: 41506

American (AMR) AF: 0.305 AC: 4652 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3466

East Asian (EAS) AF: 0.316 AC: 1640 AN: 5182

South Asian (SAS) AF: 0.326 AC: 1570 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2980 AN: 10546

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21133 AN: 67984

Other (OTH) AF: 0.262 AC: 553 AN: 2110

Alfa AF: 0.287 Hom.: 8376

Bravo AF: 0.251

Asia WGS AF: 0.278 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8031897; hg19: chr15-66646091;