chr20-19870811-T-G

Position:

• chr20-19870811-T-G

Variant summary

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

The NM_018993.4(RIN2):​c.-36-18755T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,106 control chromosomes in the GnomAD database, including 55,976 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 0.86 (55976 hom., cov: 31)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

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]

RIN2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• 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	Protein	UniProt
RIN2	NM_018993.4	c.-36-18755T>G		intron_variant		ENST00000255006.12	NP_061866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIN2	ENST00000255006.12	c.-36-18755T>G		intron_variant		2	NM_018993.4	ENSP00000255006.7
RIN2	ENST00000432334.2	n.537-18755T>G		intron_variant		4
RIN2	ENST00000616029.2	n.359-33T>G		intron_variant		6
RIN2	ENST00000648165.1	n.404-271T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130188 AN: 151988 Hom.: 55928 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.857 AC: 130298 AN: 152106 Hom.: 55976 Cov.: 31 AF XY: 0.856 AC XY: 63634 AN XY: 74348

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.847

Alfa AF: 0.831 Hom.: 108398

Bravo AF: 0.865

Asia WGS AF: 0.875 AC: 3045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.9
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4813376; hg19: chr20-19851455;