rs1000141

Variant names:

• chr2-233333701-C-T
• rs1000141
• NM_000541.5:c.807-1261C>T

Variant summary

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

The NM_000541.5(SAG):​c.807-1261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,018 control chromosomes in the GnomAD database, including 13,587 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 0.39 (13582 hom., cov: 31)
  • Exomes 𝑓: 0.46 (5 hom.)
• Consequence: SAG NM_000541.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 15 publications found

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]

SAG Gene-Disease associations (from GenCC):

• retinitis pigmentosa 47

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Oguchi disease-1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 96

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinal disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Oguchi disease

  Inheritance: AR 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAG	NM_000541.5	c.807-1261C>T		intron_variant	Intron 10 of 15	ENST00000409110.6	NP_000532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAG	ENST00000409110.6	c.807-1261C>T		intron_variant	Intron 10 of 15	5	NM_000541.5	ENSP00000386444.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58970 AN: 151850 Hom.: 13590 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.460 AC: 23 AN: 50 Hom.: 5 Cov.: 0 AF XY: 0.500 AC XY: 19 AN XY: 38

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.447 AC: 17 AN: 38

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.388 AC: 58955 AN: 151968 Hom.: 13582 Cov.: 31 AF XY: 0.389 AC XY: 28880 AN XY: 74250

African (AFR) AF: 0.138 AC: 5736 AN: 41506

American (AMR) AF: 0.357 AC: 5455 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2034 AN: 5144

South Asian (SAS) AF: 0.568 AC: 2729 AN: 4806

European-Finnish (FIN) AF: 0.456 AC: 4792 AN: 10504

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34900 AN: 67944

Other (OTH) AF: 0.408 AC: 860 AN: 2110

Alfa AF: 0.475 Hom.: 79023

Bravo AF: 0.366

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.29
PhyloP100		-0.46
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: rs1000141; hg19: chr2-234242347;