chr20-19886612-C-CTTTT

Variant names:

• chr20-19886612-C-CTTTT
• rs11362637
• NM_018993.4:c.-36-2938_-36-2935dupTTTT

Variant summary

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

The NM_018993.4(RIN2):​c.-36-2938_-36-2935dupTTTT 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 0.00062 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (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 afr. gnomad4 allele frequency = 0.000616 (71/115238) while in subpopulation AFR AF= 0.00119 (35/29370). AF 95% confidence interval is 0.00088. There are 0 homozygotes in gnomad4. There are 37 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.-36-2938_-36-2935dupTTTT		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.-36-2938_-36-2935dupTTTT		intron_variant	Intron 2 of 12	2	NM_018993.4	ENSP00000255006.7
RIN2	ENST00000648440	c.-189_-186dupTTTT		5_prime_UTR_variant	Exon 1 of 12			ENSP00000498085.1
RIN2	ENST00000432334.2	n.537-2938_537-2935dupTTTT		intron_variant	Intron 3 of 3	4
RIN2	ENST00000648165.1	n.618-2938_618-2935dupTTTT		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.000616 AC: 71 AN: 115238 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000982

Gnomad SAS AF: 0.000879

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000419

Gnomad OTH AF: 0.000653

GnomAD4 exome AF: 0.00111 AC: 449 AN: 405444 Hom.: 0 Cov.: 0 AF XY: 0.00114 AC XY: 250 AN XY: 219070

Gnomad4 AFR exome AF: 0.00199

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00100

Gnomad4 EAS exome AF: 0.00177

Gnomad4 SAS exome AF: 0.00246

Gnomad4 FIN exome AF: 0.000213

Gnomad4 NFE exome AF: 0.000885

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.000616 AC: 71 AN: 115238 Hom.: 0 Cov.: 0 AF XY: 0.000683 AC XY: 37 AN XY: 54180

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.000367

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000982

Gnomad4 SAS AF: 0.000879

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000419

Gnomad4 OTH AF: 0.000653

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;