rs2273000

Positions:

• chr6-35510691-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003322.6(TULP1):​c.499+170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,479,420 control chromosomes in the GnomAD database, including 339,927 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 0.65 (32135 hom., cov: 31)
  • Exomes 𝑓: 0.68 (307792 hom.)
• Consequence: TULP1 NM_003322.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP1	NM_003322.6	c.499+170T>C		intron_variant		ENST00000229771.11
TULP1	NM_001289395.2	c.340+170T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP1	ENST00000229771.11	c.499+170T>C		intron_variant		1	NM_003322.6	P4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98389 AN: 151916 Hom.: 32110 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.680 AC: 902986 AN: 1327386 Hom.: 307792 Cov.: 20 AF XY: 0.680 AC XY: 445290 AN XY: 655036

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.662

Gnomad4 EAS exome AF: 0.696

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.669

GnomAD4 genome AF: 0.648 AC: 98454 AN: 152034 Hom.: 32135 Cov.: 31 AF XY: 0.651 AC XY: 48376 AN XY: 74302

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.639

Alfa AF: 0.672 Hom.: 4284

Bravo AF: 0.637

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs2273000; hg19: chr6-35478468; COSMIC: COSV57694280; COSMIC: COSV57694280;