15-66386581-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001398281.1(TIPIN):​c.-9+69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TIPIN NM_001398281.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPIN	NM_001398281.1	c.-9+69T>C		intron_variant	Intron 1 of 7		NP_001385210.1
TIPIN	NM_001398283.1	c.-9+26T>C		intron_variant	Intron 1 of 7		NP_001385212.1
TIPIN	NM_001398285.1	c.-236+69T>C		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>C		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000458117.1
TIPIN	ENST00000562124.5	c.-9+26T>C		intron_variant	Intron 1 of 7	5		ENSP00000457406.1
TIPIN	ENST00000568216.5	c.-9+69T>C		intron_variant	Intron 1 of 4	3		ENSP00000457172.1
TIPIN	ENST00000561773.1	n.58+69T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.53

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;