1-241354678-T-G

Variant names:

• chr1-241354678-T-G
• rs1341467
• NM_001364886.1:c.78+1021A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001350113.2(RGS7):​c.-102A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: RGS7 NM_001350113.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 2 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350113.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	NM_001364886.1	MANE Select	c.78+1021A>C		intron	N/A	NP_001351815.1	P49802-1
	RGS7	NM_001350113.2		c.-102A>C		splice_region	Exon 3 of 19	NP_001337042.1	B7Z257
	RGS7	NM_001350115.2		c.-102A>C		splice_region	Exon 3 of 18	NP_001337044.1	A0A8I5KXW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.78+1021A>C		intron	N/A	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.78+1021A>C		intron	N/A	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.78+1021A>C		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 2

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

Other links and lift over

dbSNP: rs1341467; hg19: chr1-241517978;