17-17792953-A-G

Position:

• chr17-17792953-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_030665.4(RAI1):​c.5A>G​(p.Gln2Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 1,313,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000053 (0 hom.)
• Consequence: RAI1 NM_030665.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.67

Genes affected

RAI1 (HGNC:9834): (retinoic acid induced 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-17792953-A-G is Benign according to our data. Variant chr17-17792953-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1377204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI1	NM_030665.4	c.5A>G	p.Gln2Arg	missense_variant	3/6	ENST00000353383.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI1	ENST00000353383.6	c.5A>G	p.Gln2Arg	missense_variant	3/6	1	NM_030665.4	P1
RAI1	ENST00000395774.1	c.5A>G	p.Gln2Arg	missense_variant	2/2	2
RAI1	ENST00000471135.2	c.5A>G	p.Gln2Arg	missense_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000533 AC: 7 AN: 1313450 Hom.: 0 Cov.: 42 AF XY: 0.00000612 AC XY: 4 AN XY: 653250

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000688

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;D;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.6	M;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	N;.;D;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.99	D;.;.;.
Vest4		0.57
MutPred		0.23		Gain of MoRF binding (P = 0.0552);Gain of MoRF binding (P = 0.0552);Gain of MoRF binding (P = 0.0552);Gain of MoRF binding (P = 0.0552);
MVP		0.76
MPC		0.97
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.50
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-17696267;