rs7111480

Variant names:

• chr11-121166559-G-A
• rs7111480
• NM_005422.4:c.5384-19G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-121166559-G-A
• chr11-121166559-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005422.4(TECTA):​c.5384-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,613,856 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (33 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.11
• Publications: 1 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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-121166559-G-A is Benign according to our data. Variant chr11-121166559-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0058 (883/152262) while in subpopulation AFR AF = 0.0148 (615/41544). AF 95% confidence interval is 0.0138. There are 6 homozygotes in GnomAd4. There are 425 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

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.5384-19G>A		intron	N/A	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.6326-19G>A		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.5384-19G>A		intron	N/A	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.5384-19G>A		intron	N/A	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.5369-19G>A		intron	N/A	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 881 AN: 152144 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00767

GnomAD2 exomes AF: 0.00335 AC: 841 AN: 251266 AF XY: 0.00312

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00218

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00220 AC: 3219 AN: 1461594 Hom.: 33 Cov.: 31 AF XY: 0.00221 AC XY: 1604 AN XY: 727102

African (AFR) AF: 0.0165 AC: 553 AN: 33476

American (AMR) AF: 0.00201 AC: 90 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 526 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00174 AC: 150 AN: 86236

European-Finnish (FIN) AF: 0.0000750 AC: 4 AN: 53356

Middle Eastern (MID) AF: 0.0507 AC: 292 AN: 5764

European-Non Finnish (NFE) AF: 0.00118 AC: 1314 AN: 1111836

Other (OTH) AF: 0.00480 AC: 290 AN: 60372

GnomAD4 genome AF: 0.00580 AC: 883 AN: 152262 Hom.: 6 Cov.: 32 AF XY: 0.00571 AC XY: 425 AN XY: 74446

African (AFR) AF: 0.0148 AC: 615 AN: 41544

American (AMR) AF: 0.00281 AC: 43 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00181 AC: 123 AN: 68020

Other (OTH) AF: 0.00759 AC: 16 AN: 2108

Alfa AF: 0.00637 Hom.: 3

Bravo AF: 0.00626

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0040
DANN	Benign	0.77
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs7111480; hg19: chr11-121037268;