rs6689169

Positions:

• chr1-240775117-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000653456.1(ENSG00000226919):​n.670-688A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,168 control chromosomes in the GnomAD database, including 3,034 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 0.17 (3034 hom., cov: 32)
• Consequence: ENST00000653456.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

(HGNC:):

RGS7 (HGNC:10003): (regulator of G protein signaling 7) Enables G-protein beta-subunit binding activity and GTPase activator activity. Involved in positive regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7	NM_001374806.1	c.*1103T>C		3_prime_UTR_variant	17/17		NP_001361735.1
RGS7	NM_001374807.1	c.*1046T>C		3_prime_UTR_variant	16/16		NP_001361736.1
RGS7	NM_001374808.1	c.*1103T>C		3_prime_UTR_variant	19/19		NP_001361737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000653456.1	n.670-688A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26158 AN: 152050 Hom.: 3023 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.172 AC: 26204 AN: 152168 Hom.: 3034 Cov.: 32 AF XY: 0.167 AC XY: 12456 AN XY: 74416

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.155

Alfa AF: 0.134 Hom.: 761

Bravo AF: 0.180

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6689169; hg19: chr1-240938417;