11-77172733-C-T

Position:

• chr11-77172733-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000260.4(MYO7A):​c.1798-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,550,924 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (12 hom.)
• Consequence: MYO7A NM_000260.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.208

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-77172733-C-T is Benign according to our data. Variant chr11-77172733-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178624.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 = 0.00739 (1125/152334) while in subpopulation AFR AF= 0.0259 (1078/41578). AF 95% confidence interval is 0.0246. There are 18 homozygotes in gnomad4. There are 541 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4	c.1798-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9	c.1798-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000260.4
MYO7A	ENST00000409619.6	c.1765-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1
MYO7A	ENST00000458637.6	c.1798-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1		P1
MYO7A	ENST00000669443.1	c.162-15C>T		splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1123 AN: 152216 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00178 AC: 276 AN: 155418 Hom.: 4 AF XY: 0.00156 AC XY: 129 AN XY: 82848

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000904

Gnomad SAS exome AF: 0.000307

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000824

Gnomad OTH exome AF: 0.000690

GnomAD4 exome AF: 0.000797 AC: 1115 AN: 1398590 Hom.: 12 Cov.: 31 AF XY: 0.000698 AC XY: 482 AN XY: 690158

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.000240

Gnomad4 FIN exome AF: 0.0000209

Gnomad4 NFE exome AF: 0.0000741

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00739 AC: 1125 AN: 152334 Hom.: 18 Cov.: 33 AF XY: 0.00726 AC XY: 541 AN XY: 74494

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00920 Hom.: 2

Bravo AF: 0.00836

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

1798-15C>T in Intron 15 of MYO7A: This variant is not expected to have clinical significance because it has been identified in 2.3% (74/3190) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs115708180). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.76

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: rs115708180; hg19: chr11-76883779;