rs6046396

chr20-19871859-G-Achr20-19871859-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018993.4(RIN2):c.-36-17707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,048 control chromosomes in the GnomAD database, including 35,544 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 0.68 (35543 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4	c.-36-17707G>A		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-17707G>A		intron_variant		2	NM_018993.4	P1
RIN2	ENST00000616029.2	n.1208G>A		non_coding_transcript_exon_variant	4/4
RIN2	ENST00000432334.2	n.537-17707G>A		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.617+564G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103735 AN: 151926 Hom.: 35520 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.683 AC: 103813 AN: 152046 Hom.: 35543 Cov.: 32 AF XY: 0.679 AC XY: 50484 AN XY: 74342

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.654

Alfa AF: 0.694 Hom.: 79961

Bravo AF: 0.677

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6046396; hg19: chr20-19852503;