20-19843749-C-T

Position:

• chr20-19843749-C-T

Variant summary

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

The NM_018993.4(RIN2):​c.-37+44002C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 152,014 control chromosomes in the GnomAD database, including 288 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 0.055 (288 hom., cov: 32)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4	c.-37+44002C>T		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12	c.-37+44002C>T		intron_variant		2	NM_018993.4	P1
RIN2	ENST00000432334.2	n.536+28451C>T		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000616029.2	n.359-27095C>T		intron_variant, non_coding_transcript_variant
RIN2	ENST00000648165.1	n.404-27333C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8376 AN: 151898 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0551 AC: 8376 AN: 152014 Hom.: 288 Cov.: 32 AF XY: 0.0576 AC XY: 4279 AN XY: 74306

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0691 Hom.: 211

Bravo AF: 0.0511

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10485594; hg19: chr20-19824393;