20-19925071-C-T

Variant names:

• chr20-19925071-C-T
• rs369005
• NM_018993.4:c.58-10028C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018993.4(RIN2):​c.58-10028C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 147,382 control chromosomes in the GnomAD database, including 14,226 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14226 hom., cov: 24)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 8 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, Genomics England PanelApp, Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN2	NM_018993.4	c.58-10028C>T		intron_variant	Intron 3 of 12	ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12	c.58-10028C>T		intron_variant	Intron 3 of 12	2	NM_018993.4	ENSP00000255006.7

Frequencies

GnomAD3 genomes AF: 0.434 AC: 63957 AN: 147298 Hom.: 14220 Cov.: 24

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.457

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.434 AC: 63981 AN: 147382 Hom.: 14226 Cov.: 24 AF XY: 0.434 AC XY: 31027 AN XY: 71472

African (AFR) AF: 0.361 AC: 14293 AN: 39556

American (AMR) AF: 0.389 AC: 5759 AN: 14790

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1572 AN: 3450

East Asian (EAS) AF: 0.569 AC: 2768 AN: 4866

South Asian (SAS) AF: 0.494 AC: 2289 AN: 4634

European-Finnish (FIN) AF: 0.458 AC: 4357 AN: 9508

Middle Eastern (MID) AF: 0.439 AC: 123 AN: 280

European-Non Finnish (NFE) AF: 0.464 AC: 31252 AN: 67368

Other (OTH) AF: 0.441 AC: 893 AN: 2026

Alfa AF: 0.450 Hom.: 59517

Bravo AF: 0.422

Asia WGS AF: 0.512 AC: 1780 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.60
PhyloP100		-0.24
Mutation Taster		=100/0	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: rs369005; hg19: chr20-19905715;