NM_018993.4:c.-36-2936_-36-2935delTT

Variant names:

• chr20-19886612-CTT-C
• rs11362637
• NM_018993.4:c.-36-2936_-36-2935delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018993.4(RIN2):​c.-36-2936_-36-2935delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 506,436 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 0)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN2	NM_018993.4	c.-36-2936_-36-2935delTT		intron_variant	Intron 2 of 12	ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-2936_-36-2935delTT		intron_variant	Intron 2 of 12	2	NM_018993.4	ENSP00000255006.7
RIN2	ENST00000648440	c.-187_-186delTT		5_prime_UTR_variant	Exon 1 of 12			ENSP00000498085.1
RIN2	ENST00000432334.2	n.537-2936_537-2935delTT		intron_variant	Intron 3 of 3	4
RIN2	ENST00000648165.1	n.618-2936_618-2935delTT		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.000590 AC: 68 AN: 115258 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000734

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000737

Gnomad SAS AF: 0.000586

Gnomad FIN AF: 0.00257

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.000653

GnomAD4 exome AF: 0.135 AC: 52666 AN: 391190 Hom.: 1 AF XY: 0.133 AC XY: 28204 AN XY: 211316

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.000599 AC: 69 AN: 115246 Hom.: 0 Cov.: 0 AF XY: 0.000554 AC XY: 30 AN XY: 54194

Gnomad4 AFR AF: 0.000748

Gnomad4 AMR AF: 0.000734

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000740

Gnomad4 SAS AF: 0.000590

Gnomad4 FIN AF: 0.00257

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.000649

ClinVar

Not reported in ClinVar

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;