rs2186747

Variant names:

• chr11-121166820-C-G
• rs2186747
• NM_005422.4:c.5586+40C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-121166820-C-G
• chr11-121166820-C-T

Variant summary

Our verdict is Benign. The variant received -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 (★★). The gene TECTA is included in the ClinGen Criteria Specification Registry.

• 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:4
• Conservation: PhyloP100: -1.79
• Publications: 5 publications found

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:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Specifications for TECTA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.5586+40C>G		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6528+40C>G		intron	N/A	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.5586+40C>G		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5586+40C>G		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5571+40C>G		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

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

GnomAD2 exomes AF: 0.233 AC: 57633 AN: 246908 AF XY: 0.237

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 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

African (AFR) AF: 0.0420 AC: 1405 AN: 33432

American (AMR) AF: 0.187 AC: 8373 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6874 AN: 26114

East Asian (EAS) AF: 0.259 AC: 10259 AN: 39672

South Asian (SAS) AF: 0.228 AC: 19562 AN: 85734

European-Finnish (FIN) AF: 0.281 AC: 13900 AN: 49544

Middle Eastern (MID) AF: 0.179 AC: 1030 AN: 5756

European-Non Finnish (NFE) AF: 0.272 AC: 302148 AN: 1110048

Other (OTH) AF: 0.244 AC: 14676 AN: 60260

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

African (AFR) AF: 0.0516 AC: 2142 AN: 41548

American (AMR) AF: 0.183 AC: 2794 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5174

South Asian (SAS) AF: 0.206 AC: 992 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2875 AN: 10572

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18113 AN: 67994

Other (OTH) AF: 0.190 AC: 400 AN: 2108

Alfa AF: 0.178 Hom.: 571

Bravo AF: 0.182

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 12 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.60
PhyloP100		-1.8
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: rs2186747; hg19: chr11-121037529; COSMIC: COSV50693747;