NM_020829.4:c.145-9delA

Variant names:

• chr9-5656572-TA-T
• rs765295308
• NM_020829.4:c.145-9delA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_020829.4(RIC1):​c.145-9delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,377,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RIC1 NM_020829.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.760
• Publications: 0 publications found

Genes affected

RIC1 (HGNC:17686): (RIC1 homolog, RAB6A GEF complex partner 1) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Apr 2022]

RIC1 Gene-Disease associations (from GenCC):

• Catifa syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 9-5656572-TA-T is Benign according to our data. Variant chr9-5656572-TA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3036783.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020829.4. 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
	RIC1	NM_020829.4	MANE Select	c.145-9delA		intron	N/A	NP_065880.2	Q4ADV7-1
	RIC1	NM_001206557.2		c.145-9delA		intron	N/A	NP_001193486.1	Q4ADV7-3
	RIC1	NM_001135920.4		c.145-9delA		intron	N/A	NP_001129392.2	Q4ADV7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC1	ENST00000414202.7	TSL:5 MANE Select	c.145-9delA		intron	N/A	ENSP00000416696.2	Q4ADV7-1
	RIC1	ENST00000251879.10	TSL:1	c.145-9delA		intron	N/A	ENSP00000251879.6	Q4ADV7-2
	RIC1	ENST00000894135.1		c.145-9delA		intron	N/A	ENSP00000564194.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151386 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000635 AC: 12 AN: 188850 AF XY: 0.0000578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000655

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 17 AN: 1226254 Hom.: 0 Cov.: 17 AF XY: 0.0000164 AC XY: 10 AN XY: 610970

⚠️ 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: 26734

American (AMR) AF: 0.000573 AC: 16 AN: 27906

Ashkenazi Jewish (ASJ) AF: 0.0000474 AC: 1 AN: 21114

East Asian (EAS) AF: 0.00 AC: 0 AN: 37042

South Asian (SAS) AF: 0.00 AC: 0 AN: 63946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5028

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 945316

Other (OTH) AF: 0.00 AC: 0 AN: 50870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000508225), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151386 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73960

African (AFR) AF: 0.00 AC: 0 AN: 40884

American (AMR) AF: 0.000197 AC: 3 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RIC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs765295308; hg19: chr9-5656572;