1-216078074-C-T

Variant names:

• chr1-216078074-C-T
• rs17026052
• NM_206933.4:c.5572+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000307340.8(USH2A):​c.5572+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,358 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (29 hom.)
• Consequence: USH2A ENST00000307340.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.681
• Publications: 0 publications found

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

USH2A-AS2 (HGNC:40605): (USH2A antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-216078074-C-T is Benign according to our data. Variant chr1-216078074-C-T is described in ClinVar as Benign. ClinVar VariationId is 48534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1695/152194) while in subpopulation AFR AF = 0.0392 (1628/41526). AF 95% confidence interval is 0.0376. There are 33 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307340.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.5572+15G>A		intron	N/A	NP_996816.3
	USH2A-AS2	NR_125992.1		n.137-999C>T		intron	N/A
	USH2A-AS2	NR_125993.1		n.136+5474C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.5572+15G>A		intron	N/A	ENSP00000305941.3
	USH2A	ENST00000674083.1		c.5572+15G>A		intron	N/A	ENSP00000501296.1
	USH2A-AS2	ENST00000430890.5	TSL:2	n.79-999C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1690 AN: 152076 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00272 AC: 678 AN: 249414 AF XY: 0.00215

Gnomad AFR exome AF: 0.0377

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000447

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00112 AC: 1643 AN: 1461164 Hom.: 29 Cov.: 32 AF XY: 0.000937 AC XY: 681 AN XY: 726876

African (AFR) AF: 0.0418 AC: 1396 AN: 33432

American (AMR) AF: 0.00125 AC: 56 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5736

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111598

Other (OTH) AF: 0.00265 AC: 160 AN: 60340

GnomAD4 genome AF: 0.0111 AC: 1695 AN: 152194 Hom.: 33 Cov.: 32 AF XY: 0.0110 AC XY: 818 AN XY: 74404

African (AFR) AF: 0.0392 AC: 1628 AN: 41526

American (AMR) AF: 0.00301 AC: 46 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00491 Hom.: 3

Bravo AF: 0.0125

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa 39 (1)
-	-	1	Usher syndrome type 2A (1)
-	-	1	Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism

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: rs17026052; hg19: chr1-216251416;