chr20-19886612-CT-C

Position:

• chr20-19886612-CT-C

Variant summary

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

The NM_018993.4(RIN2):​c.-36-2935del 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

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-CT-C is Benign according to our data. Variant chr20-19886612-CT-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

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

Ensembl

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

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

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.281

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.347

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 16, 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;