chr20-19886612-C-CTTT

Variant names:

• chr20-19886612-C-CTTT
• rs11362637
• NM_018993.4:c.-36-2937_-36-2935dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_018993.4(RIN2):​c.-36-2937_-36-2935dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000686 (79/115164) while in subpopulation NFE AF= 0.000927 (53/57196). AF 95% confidence interval is 0.000727. There are 0 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN2	NM_018993.4	c.-36-2937_-36-2935dupTTT		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.-36-2937_-36-2935dupTTT		intron_variant	Intron 2 of 12	2	NM_018993.4	ENSP00000255006.7
RIN2	ENST00000648440	c.-188_-186dupTTT		5_prime_UTR_variant	Exon 1 of 12			ENSP00000498085.1
RIN2	ENST00000432334.2	n.537-2937_537-2935dupTTT		intron_variant	Intron 3 of 3	4
RIN2	ENST00000648165.1	n.618-2937_618-2935dupTTT		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.000686 AC: 79 AN: 115176 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000443

Gnomad AMI AF: 0.00126

Gnomad AMR AF: 0.000275

Gnomad ASJ AF: 0.00200

Gnomad EAS AF: 0.000245

Gnomad SAS AF: 0.000586

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000927

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00161 AC: 654 AN: 405432 Hom.: 0 Cov.: 0 AF XY: 0.00168 AC XY: 368 AN XY: 219068

Gnomad4 AFR exome AF: 0.00223

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.00355

Gnomad4 FIN exome AF: 0.000579

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.000686 AC: 79 AN: 115164 Hom.: 0 Cov.: 0 AF XY: 0.000812 AC XY: 44 AN XY: 54154

Gnomad4 AFR AF: 0.000442

Gnomad4 AMR AF: 0.000275

Gnomad4 ASJ AF: 0.00200

Gnomad4 EAS AF: 0.000246

Gnomad4 SAS AF: 0.000590

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000927

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;