20-19886612-C-CT

Position:

• chr20-19886612-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.14 (1241 hom., cov: 0)
  • Exomes 𝑓: 0.045 (11 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.844

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-19886612-C-CT is Benign according to our data. Variant chr20-19886612-C-CT is described in ClinVar as [Benign]. Clinvar id is 1276958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIN2	NM_018993.4	c.-36-2935dup		intron_variant		ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-2935dup		intron_variant		2	NM_018993.4	ENSP00000255006	P1
RIN2	ENST00000648440.1	c.-186dup		5_prime_UTR_variant	1/12			ENSP00000498085	P1
RIN2	ENST00000432334.2	n.537-2935dup		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.618-2935dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.138 AC: 15920 AN: 115156 Hom.: 1242 Cov.: 0

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0949

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.0453 AC: 18255 AN: 403032 Hom.: 11 Cov.: 0 AF XY: 0.0443 AC XY: 9650 AN XY: 217770

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.0426

Gnomad4 EAS exome AF: 0.0817

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0328

Gnomad4 NFE exome AF: 0.0410

Gnomad4 OTH exome AF: 0.0506

GnomAD4 genome AF: 0.138 AC: 15924 AN: 115142 Hom.: 1241 Cov.: 0 AF XY: 0.140 AC XY: 7600 AN XY: 54146

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0693

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.144

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11362637; hg19: chr20-19867256;