chr20-19886282-G-A

Position:

• chr20-19886282-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018993.4(RIN2):​c.-36-3284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 152,240 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.039 (145 hom., cov: 32)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.41

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-19886282-G-A is Benign according to our data. Variant chr20-19886282-G-A is described in ClinVar as [Benign]. Clinvar id is 669475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIN2	NM_018993.4	c.-36-3284G>A		intron_variant		ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-3284G>A		intron_variant		2	NM_018993.4	ENSP00000255006	P1
RIN2	ENST00000432334.2	n.537-3284G>A		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.618-3284G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5932 AN: 152122 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0503

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0390 AC: 5930 AN: 152240 Hom.: 145 Cov.: 32 AF XY: 0.0395 AC XY: 2942 AN XY: 74432

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.0668

Gnomad4 SAS AF: 0.0866

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.0245

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0307 Hom.: 16

Bravo AF: 0.0412

Asia WGS AF: 0.0710 AC: 245 AN: 3478

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

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.029
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75113125; hg19: chr20-19866926;