10-68232096-A-G

Position:

• chr10-68232096-A-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.-419T>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 0.6 in 166,832 control chromosomes in the GnomAD database, including 33,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (30038 hom., cov: 32)
  • Exomes 𝑓: 0.68 (3397 hom.)
• Consequence: ATOH7 NM_145178.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.704

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=-0.54).
• BP6: Variant 10-68232096-A-G is Benign according to our data. Variant chr10-68232096-A-G is described in ClinVar as [Benign]. Clinvar id is 1237376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATOH7	NM_145178.4	c.-419T>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.-419T>C		5_prime_UTR_variant	1/1	6	NM_145178.4	ENSP00000362777.3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90156 AN: 152012 Hom.: 30037 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.679 AC: 9982 AN: 14702 Hom.: 3397 Cov.: 0 AF XY: 0.674 AC XY: 4689 AN XY: 6960

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.761

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.593 AC: 90185 AN: 152130 Hom.: 30038 Cov.: 32 AF XY: 0.591 AC XY: 43947 AN XY: 74346

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.640

Alfa AF: 0.720 Hom.: 73754

Bravo AF: 0.570

Asia WGS AF: 0.683 AC: 2373 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	-0.54
CADD	Benign	14
DANN	Benign	0.86

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: rs7916697; hg19: chr10-69991853;