rs6689169

Variant names:

• chr1-240775117-A-G
• rs6689169
• ENST00000687018.1:n.*2365T>C

Variant summary

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

The ENST00000687018.1(RGS7):​n.*2365T>C variant causes a non coding transcript exon 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: RGS7 ENST00000687018.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 publications found

Genes affected

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]

RGS7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000226919 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RGS7	NM_001374806.1	c.*1103T>C		3_prime_UTR_variant	Exon 17 of 17		NP_001361735.1
RGS7	NM_001374807.1	c.*1046T>C		3_prime_UTR_variant	Exon 16 of 16		NP_001361736.1
RGS7	NM_001374808.1	c.*1103T>C		3_prime_UTR_variant	Exon 19 of 19		NP_001361737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000687018.1	n.*2365T>C		non_coding_transcript_exon_variant	Exon 18 of 18			ENSP00000509943.1
RGS7	ENST00000687018.1	n.*2365T>C		3_prime_UTR_variant	Exon 18 of 18			ENSP00000509943.1
RGS7	ENST00000690539.1	c.1360-6839T>C		intron_variant	Intron 16 of 16			ENSP00000510322.1

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

African (AFR) AF: 0.330 AC: 13703 AN: 41462

American (AMR) AF: 0.0974 AC: 1488 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5174

South Asian (SAS) AF: 0.102 AC: 494 AN: 4826

European-Finnish (FIN) AF: 0.0772 AC: 820 AN: 10622

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8172 AN: 68016

Other (OTH) AF: 0.155 AC: 328 AN: 2110

Alfa AF: 0.164 Hom.: 2000

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6689169; hg19: chr1-240938417;