Genetic Variant ATOH7:c.-419T>C (chr10-68232096-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.704

Variant links:

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]

ATOH7 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ATOH7	NM_145178.4 link	c.-419T>C		5_prime_UTR_variant	Exon 1 of 1	ENST00000373673.5	NP_660161.1	Q8N100F1T0H4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH7	ENST00000373673.5 link	c.-419T>C		5_prime_UTR_variant	Exon 1 of 1	6	NM_145178.4	ENSP00000362777.3		Q8N100

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90156

AN:

152012

Hom.:

30037

Cov.:

show subpopulations

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.:

AF XY:

0.674

AC XY:

4689

AN XY:

6960

show subpopulations

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.:

AF XY:

0.591

AC XY:

43947

AN XY:

74346

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over