rs4814920

chr20-19885312-A-T

Variant summary

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

The NM_018993.4(RIN2):c.-36-4254A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,136 control chromosomes in the GnomAD database, including 51,715 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 0.82 (51715 hom., cov: 31)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIN2	NM_018993.4	c.-36-4254A>T		intron_variant		ENST00000255006.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-4254A>T		intron_variant		2	NM_018993.4	P1
RIN2	ENST00000432334.2	n.537-4254A>T		intron_variant, non_coding_transcript_variant		4
RIN2	ENST00000648165.1	n.618-4254A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125207 AN: 152018 Hom.: 51668 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.824 AC: 125312 AN: 152136 Hom.: 51715 Cov.: 31 AF XY: 0.824 AC XY: 61250 AN XY: 74346

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.824

Alfa AF: 0.815 Hom.: 6261

Bravo AF: 0.829

Asia WGS AF: 0.869 AC: 3021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.34
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4814920; hg19: chr20-19865956;