dbSNP rs6480320: ATOH7:c.-234C>T (chr10-68231911-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.633

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

persistent hyperplastic primary vitreous, autosomal recessive
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
persistent hyperplastic primary vitreous
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
anterior segment dysgenesis 7
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATOH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 1254659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ATOH7	NM_145178.4 link	c.-234C>T		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.-234C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_145178.4	ENSP00000362777.3		Q8N100

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9056

AN:

152164

Hom.:

926

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00456

AC XY:

138

AN XY:

30296

show subpopulations

African (AFR)

AF:

0.187

AC:

200

AN:

1072

American (AMR)

AF:

0.0174

AC:

AN:

1148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1388

East Asian (EAS)

AF:

0.00

AC:

AN:

3942

South Asian (SAS)

AF:

0.00

AC:

AN:

384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18848

Middle Eastern (MID)

AF:

0.00909

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.00146

AC:

AN:

29420

Other (OTH)

AF:

0.0188

AC:

AN:

2770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0596

AC:

9076

AN:

152282

Hom.:

928

Cov.:

AF XY:

0.0568

AC XY:

4230

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.206

AC:

8557

AN:

41534

American (AMR)

AF:

0.0229

AC:

350

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68022

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

370

741

1111

1482

1852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0600

Hom.:

291

Bravo

AF:

0.0688

Asia WGS

AF:

0.0130

AC:

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

- -

May 20, 2021

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

-0.80

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.63

PromoterAI

-0.012

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over