1-240998475-C-G

Variant names:

• chr1-240998475-C-G
• rs670659
• NM_001364886.1:c.176-15346G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364886.1(RGS7):​c.176-15346G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 844,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 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

ENSG00000238085 (HGNC:):

RPLP1P2 (HGNC:36210):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.176-15346G>C		intron_variant	Intron 3 of 18	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.176-15346G>C		intron_variant	Intron 3 of 18	1	NM_001364886.1	ENSP00000404399.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 844282 Hom.: 0 Cov.: 12 AF XY: 0.00000226 AC XY: 1 AN XY: 443420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21390

American (AMR) AF: 0.0000256 AC: 1 AN: 39104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20558

East Asian (EAS) AF: 0.00 AC: 0 AN: 35432

South Asian (SAS) AF: 0.00 AC: 0 AN: 72992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 578548

Other (OTH) AF: 0.00 AC: 0 AN: 38740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		2.3

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: rs670659; hg19: chr1-241161775;