12-71441769-C-T

Position:

• chr12-71441769-C-T

Variant summary

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

The ENST00000393330.6(TSPAN8):​c.-424G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 152,260 control chromosomes in the GnomAD database, including 189 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 0.041 (189 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TSPAN8 ENST00000393330.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

LGR5 (HGNC:4504): (leucine rich repeat containing G protein-coupled receptor 5) The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

LOC124902962 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGR5	NM_003667.4	c.212+1477C>T		intron_variant		ENST00000266674.10
LOC124902962	XR_007063364.1	n.77-182G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGR5	ENST00000266674.10	c.212+1477C>T		intron_variant		1	NM_003667.4	P1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6271 AN: 152142 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0426

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0412 AC: 6270 AN: 152260 Hom.: 189 Cov.: 32 AF XY: 0.0396 AC XY: 2946 AN XY: 74446

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0640

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0580 Hom.: 67

Bravo AF: 0.0398

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.9
DANN	Benign	0.77

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: rs77053565; hg19: chr12-71835549;