rs6480320

chr10-68231911-G-A

Variant summary

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

The NM_145178.4(ATOH7):c.-234C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 211,474 control chromosomes in the GnomAD database, including 947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (928 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (19 hom.)
• Consequence: ATOH7 NM_145178.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.633

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-68231911-G-A is Benign according to our data. Variant chr10-68231911-G-A is described in ClinVar as [Benign]. Clinvar id is 1254659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATOH7	NM_145178.4	c.-234C>T		5_prime_UTR_variant	1/1	ENST00000373673.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATOH7	ENST00000373673.5	c.-234C>T		5_prime_UTR_variant	1/1		NM_145178.4	P1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9056 AN: 152164 Hom.: 926 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.00536 AC: 317 AN: 59192 Hom.: 19 Cov.: 3 AF XY: 0.00456 AC XY: 138 AN XY: 30296

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0174

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0596 AC: 9076 AN: 152282 Hom.: 928 Cov.: 33 AF XY: 0.0568 AC XY: 4230 AN XY: 74482

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0576 Hom.: 276

Bravo AF: 0.0688

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	14
Dann	Benign	0.63

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: rs6480320; hg19: chr10-69991668;