10-68232096-A-G

Variant names:

• chr10-68232096-A-G
• rs7916697
• NM_145178.4:c.-419T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.-419T>C		5_prime_UTR_variant	Exon 1 of 1	ENST00000373673.5	NP_660161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH7	ENST00000373673.5	c.-419T>C		5_prime_UTR_variant	Exon 1 of 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

African (AFR) AF: 0.462 AC: 12 AN: 26

American (AMR) AF: 0.500 AC: 4 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 4 AN: 8

East Asian (EAS) AF: 0.500 AC: 17 AN: 34

South Asian (SAS) AF: 0.875 AC: 7 AN: 8

European-Finnish (FIN) AF: 0.678 AC: 9596 AN: 14160

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.761 AC: 251 AN: 330

Other (OTH) AF: 0.706 AC: 89 AN: 126

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

African (AFR) AF: 0.269 AC: 11148 AN: 41492

American (AMR) AF: 0.639 AC: 9766 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3470

East Asian (EAS) AF: 0.654 AC: 3379 AN: 5166

South Asian (SAS) AF: 0.708 AC: 3409 AN: 4814

European-Finnish (FIN) AF: 0.681 AC: 7203 AN: 10576

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51029 AN: 68006

Other (OTH) AF: 0.640 AC: 1354 AN: 2114

Alfa AF: 0.699 Hom.: 168100

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

-

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	14
DANN	Benign	0.86
PhyloP100		0.70
PromoterAI		0.0031	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7916697; hg19: chr10-69991853;