rs1000548

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000541.5(SAG):​c.436-465T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 151,706 control chromosomes in the GnomAD database, including 416 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 0.067 ( 416 hom., cov: 31)

Consequence

SAG
NM_000541.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25
Variant links:
Genes affected
SAG (HGNC:10521): (S-antigen visual arrestin) Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0985 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SAGNM_000541.5 linkuse as main transcriptc.436-465T>C intron_variant ENST00000409110.6 NP_000532.2 P10523

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SAGENST00000409110.6 linkuse as main transcriptc.436-465T>C intron_variant 5 NM_000541.5 ENSP00000386444.1 P10523

Frequencies

GnomAD3 genomes
AF:
0.0671
AC:
10177
AN:
151654
Hom.:
416
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.101
Gnomad AMI
AF:
0.0373
Gnomad AMR
AF:
0.0440
Gnomad ASJ
AF:
0.0612
Gnomad EAS
AF:
0.0228
Gnomad SAS
AF:
0.105
Gnomad FIN
AF:
0.0835
Gnomad MID
AF:
0.0321
Gnomad NFE
AF:
0.0508
Gnomad OTH
AF:
0.0639
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0671
AC:
10186
AN:
151706
Hom.:
416
Cov.:
31
AF XY:
0.0682
AC XY:
5052
AN XY:
74062
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.0439
Gnomad4 ASJ
AF:
0.0612
Gnomad4 EAS
AF:
0.0231
Gnomad4 SAS
AF:
0.104
Gnomad4 FIN
AF:
0.0835
Gnomad4 NFE
AF:
0.0508
Gnomad4 OTH
AF:
0.0672
Alfa
AF:
0.0576
Hom.:
66
Bravo
AF:
0.0645
Asia WGS
AF:
0.0880
AC:
306
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
0.23
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1000548; hg19: chr2-234235302; API