11-77183418-C-T

Variant names:

• chr11-77183418-C-T
• rs3758708
• NM_000260.4:c.3375+261C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000260.4(MYO7A):​c.3375+261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,174 control chromosomes in the GnomAD database, including 762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.095 (762 hom., cov: 32)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-77183418-C-T is Benign according to our data. Variant chr11-77183418-C-T is described in ClinVar as [Benign]. Clinvar id is 1288435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3375+261C>T		intron_variant	Intron 26 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3375+261C>T		intron_variant	Intron 26 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3375+261C>T		intron_variant	Intron 26 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3342+261C>T		intron_variant	Intron 27 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.918+261C>T		intron_variant	Intron 6 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1215+261C>T		intron_variant	Intron 9 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14384 AN: 152056 Hom.: 762 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0500

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.0920

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0946 AC: 14402 AN: 152174 Hom.: 762 Cov.: 32 AF XY: 0.0950 AC XY: 7070 AN XY: 74412

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.0500

Gnomad4 NFE AF: 0.0779

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.0809 Hom.: 600

Bravo AF: 0.104

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
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: rs3758708; hg19: chr11-76894463;