20-19830470-A-T

Variant names:

• chr20-19830470-A-T
• rs2876544
• NM_018993.4:c.-37+30723A>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+30723A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,042 control chromosomes in the GnomAD database, including 2,622 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 0.18 (2622 hom., cov: 32)
• Consequence: RIN2 NM_018993.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN2	NM_018993.4	c.-37+30723A>T		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.-37+30723A>T		intron_variant	Intron 2 of 12	2	NM_018993.4	ENSP00000255006.7
RIN2	ENST00000432334.2	n.536+15172A>T		intron_variant	Intron 3 of 3	4
RIN2	ENST00000616029.2	n.358+30723A>T		intron_variant	Intron 2 of 3	6
RIN2	ENST00000648165.1	n.403+30723A>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26751 AN: 151924 Hom.: 2622 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.176 AC: 26772 AN: 152042 Hom.: 2622 Cov.: 32 AF XY: 0.173 AC XY: 12829 AN XY: 74338

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.162

Alfa AF: 0.160 Hom.: 275

Bravo AF: 0.178

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
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: rs2876544; hg19: chr20-19811114;