NM_206933.4:c.11389+3454A>G

Variant names:

• chr1-215755141-T-C
• rs11120620
• NM_206933.4:c.11389+3454A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206933.4(USH2A):​c.11389+3454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,128 control chromosomes in the GnomAD database, including 4,025 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4025 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 2 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 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 39

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4	c.11389+3454A>G		intron_variant	Intron 58 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.11389+3454A>G		intron_variant	Intron 58 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.11389+3454A>G		intron_variant	Intron 58 of 72			ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33781 AN: 152008 Hom.: 4020 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33811 AN: 152128 Hom.: 4025 Cov.: 32 AF XY: 0.223 AC XY: 16585 AN XY: 74358

African (AFR) AF: 0.309 AC: 12814 AN: 41492

American (AMR) AF: 0.152 AC: 2324 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3468

East Asian (EAS) AF: 0.107 AC: 554 AN: 5174

South Asian (SAS) AF: 0.184 AC: 887 AN: 4826

European-Finnish (FIN) AF: 0.261 AC: 2764 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12938 AN: 67994

Other (OTH) AF: 0.221 AC: 466 AN: 2112

Alfa AF: 0.188 Hom.: 4828

Bravo AF: 0.218

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.51
PhyloP100		0.018
Mutation Taster		=100/0	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: rs11120620; hg19: chr1-215928483;