rs2186747

chr11-121166820-C-Gchr11-121166820-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005422.4(TECTA):c.5586+40C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,607,404 control chromosomes in the GnomAD database, including 54,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3566 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50883 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.79

Genes affected

TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]

TBCEL-TECTA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-121166820-C-G is Benign according to our data. Variant chr11-121166820-C-G is described in ClinVar as [Benign]. Clinvar id is 1274473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECTA	NM_005422.4	c.5586+40C>G		intron_variant		ENST00000392793.6
TBCEL-TECTA	NM_001378761.1	c.6528+40C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECTA	ENST00000392793.6	c.5586+40C>G		intron_variant		5	NM_005422.4	P4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29594 AN: 152066 Hom.: 3567 Cov.: 33

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.233 AC: 57633 AN: 246908 Hom.: 7219 AF XY: 0.237 AC XY: 31663 AN XY: 133668

Gnomad AFR exome AF: 0.0450

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.260 AC: 378227 AN: 1455220 Hom.: 50883 Cov.: 31 AF XY: 0.259 AC XY: 187859 AN XY: 724056

Gnomad4 AFR exome AF: 0.0420

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.194 AC: 29584 AN: 152184 Hom.: 3566 Cov.: 33 AF XY: 0.193 AC XY: 14376 AN XY: 74376

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.190

Alfa AF: 0.178 Hom.: 571

Bravo AF: 0.182

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 21 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Autosomal dominant nonsyndromic hearing loss 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.023
Dann	Benign	0.60

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: rs2186747; hg19: chr11-121037529; COSMIC: COSV50693747;