chr20-19886608-TC-T

Position:

• chr20-19886608-TC-T

Variant summary

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

The NM_018993.4(RIN2):​c.-36-2957del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 860,530 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (28 hom., cov: 30)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86

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 20-19886608-TC-T is Benign according to our data. Variant chr20-19886608-TC-T is described in ClinVar as [Benign]. Clinvar id is 1278212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4	c.-36-2957del		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-2957del		intron_variant		2	NM_018993.4	P1
RIN2	ENST00000648440.1	c.-208del		5_prime_UTR_variant	1/12			P1
RIN2	ENST00000432334.2	n.537-2957del		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.618-2957del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 1785 AN: 125588 Hom.: 28 Cov.: 30

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000224

Gnomad OTH AF: 0.0112

GnomAD4 exome AF: 0.000235 AC: 173 AN: 734896 Hom.: 1 Cov.: 10 AF XY: 0.000211 AC XY: 81 AN XY: 384342

Gnomad4 AFR exome AF: 0.00813

Gnomad4 AMR exome AF: 0.000663

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000688

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000200

Gnomad4 OTH exome AF: 0.000711

GnomAD4 genome AF: 0.0142 AC: 1785 AN: 125634 Hom.: 28 Cov.: 30 AF XY: 0.0138 AC XY: 830 AN XY: 60160

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.00603

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000271

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000224

Gnomad4 OTH AF: 0.0110

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

Sep 19, 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: rs11476169; hg19: chr20-19867252;