20-19886612-CTTTTTTTTTTT-CTTTTTTTTTT

Variant names:

• chr20-19886612-CT-C
• rs11362637
• NM_018993.4:c.-36-2935delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018993.4(RIN2):​c.-36-2935delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (7053 hom., cov: 0)
  • Exomes 𝑓: 0.27 (216 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844
• Publications: 2 publications found

Genes affected

RIN2 (HGNC:18750): (Ras and Rab interactor 2) The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

RIN2 Gene-Disease associations (from GenCC):

• RIN2 syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-19886612-CT-C is Benign according to our data. Variant chr20-19886612-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1257379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018993.4. 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
	RIN2	NM_018993.4	MANE Select	c.-36-2935delT		intron	N/A	NP_061866.1	Q8WYP3-1
	RIN2	NM_001378238.1		c.-581-2935delT		intron	N/A	NP_001365167.1
	RIN2	NM_001242581.2		c.-57delT		upstream_gene	N/A	NP_001229510.1	Q8WYP3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIN2	ENST00000255006.12	TSL:2 MANE Select	c.-36-2935delT		intron	N/A	ENSP00000255006.7	Q8WYP3-1
	RIN2	ENST00000648440.1		c.-186delT		5_prime_UTR	Exon 1 of 12	ENSP00000498085.1	Q8WYP3-1
	RIN2	ENST00000944201.1		c.-186delT		5_prime_UTR	Exon 1 of 10	ENSP00000614260.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 43481 AN: 115110 Hom.: 7054 Cov.: 0

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.269 AC: 107749 AN: 400462 Hom.: 216 Cov.: 0 AF XY: 0.267 AC XY: 57828 AN XY: 216314

African (AFR) AF: 0.248 AC: 2065 AN: 8318

American (AMR) AF: 0.239 AC: 3858 AN: 16152

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 2925 AN: 12810

East Asian (EAS) AF: 0.297 AC: 7120 AN: 24008

South Asian (SAS) AF: 0.228 AC: 9045 AN: 39692

European-Finnish (FIN) AF: 0.231 AC: 7506 AN: 32430

Middle Eastern (MID) AF: 0.203 AC: 470 AN: 2310

European-Non Finnish (NFE) AF: 0.282 AC: 68800 AN: 243558

Other (OTH) AF: 0.281 AC: 5960 AN: 21184

GnomAD4 genome AF: 0.378 AC: 43474 AN: 115096 Hom.: 7053 Cov.: 0 AF XY: 0.375 AC XY: 20291 AN XY: 54142

African (AFR) AF: 0.294 AC: 8624 AN: 29352

American (AMR) AF: 0.368 AC: 4004 AN: 10882

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 962 AN: 2998

East Asian (EAS) AF: 0.372 AC: 1509 AN: 4058

South Asian (SAS) AF: 0.405 AC: 1371 AN: 3388

European-Finnish (FIN) AF: 0.421 AC: 1969 AN: 4680

Middle Eastern (MID) AF: 0.233 AC: 49 AN: 210

European-Non Finnish (NFE) AF: 0.422 AC: 24145 AN: 57190

Other (OTH) AF: 0.347 AC: 535 AN: 1544

Alfa AF: 0.196 Hom.: 309

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.84
Mutation Taster		=299/1	polymorphism (auto)

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: rs11362637; hg19: chr20-19867256; COSMIC: COSV107295452; COSMIC: COSV107295452;