rs61854782

Positions:

• chr10-68231992-T-G

Variant summary

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

The NM_145178.4(ATOH7):​c.-315A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 171,484 control chromosomes in the GnomAD database, including 2,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2015 hom., cov: 33)
  • Exomes 𝑓: 0.19 (333 hom.)
• Consequence: ATOH7 NM_145178.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240

Genes affected

ATOH7 (HGNC:13907): (atonal bHLH transcription factor 7) This intronless gene encodes a member of the basic helix-loop-helix family of transcription factors, with similarity to Drosophila atonal gene that controls photoreceptor development. Studies in mice suggest that this gene plays a central role in retinal ganglion cell and optic nerve formation. Mutations in this gene are associated with nonsyndromic congenital retinal nonattachment. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-68231992-T-G is Benign according to our data. Variant chr10-68231992-T-G is described in ClinVar as [Benign]. Clinvar id is 1266780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATOH7	NM_145178.4	c.-315A>C		5_prime_UTR_variant	1/1	ENST00000373673.5	NP_660161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATOH7	ENST00000373673.5	c.-315A>C		5_prime_UTR_variant	1/1		NM_145178.4	ENSP00000362777	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21304 AN: 152112 Hom.: 2012 Cov.: 33

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.194 AC: 3727 AN: 19254 Hom.: 333 Cov.: 0 AF XY: 0.198 AC XY: 1849 AN XY: 9362

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.140 AC: 21318 AN: 152230 Hom.: 2015 Cov.: 33 AF XY: 0.144 AC XY: 10731 AN XY: 74432

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.142

Alfa AF: 0.139 Hom.: 416

Bravo AF: 0.139

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61854782; hg19: chr10-69991749;