rs11362637

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_018993.4(RIN2):c.-36-2943_-36-2935delTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 405,686 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

RIN2 syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

RIN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000394 (16/405686) while in subpopulation AFR AF = 0.00082 (7/8538). AF 95% confidence interval is 0.000384. There are 0 homozygotes in GnomAdExome4. There are 8 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018993.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIN2	NM_018993.4	MANE Select	c.-36-2943_-36-2935delTTTTTTTTT	intron	N/A	NP_061866.1	Q8WYP3-1
RIN2	NM_001378238.1		c.-581-2943_-581-2935delTTTTTTTTT	intron	N/A	NP_001365167.1
RIN2	NM_001242581.2		c.-57_-49delTTTTTTTTT	upstream_gene	N/A	NP_001229510.1	Q8WYP3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIN2	ENST00000255006.12	TSL:2 MANE Select	c.-36-2943_-36-2935delTTTTTTTTT	intron	N/A	ENSP00000255006.7	Q8WYP3-1
RIN2	ENST00000648440.1		c.-194_-186delTTTTTTTTT	5_prime_UTR	Exon 1 of 12	ENSP00000498085.1	Q8WYP3-1
RIN2	ENST00000944201.1		c.-194_-186delTTTTTTTTT	5_prime_UTR	Exon 1 of 10	ENSP00000614260.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000394

AC:

AN:

405686

Hom.:

AF XY:

0.0000365

AC XY:

AN XY:

219208

show subpopulations

African (AFR)

AF:

0.000820

AC:

AN:

8538

American (AMR)

AF:

0.0000612

AC:

AN:

16344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12956

East Asian (EAS)

AF:

0.000123

AC:

AN:

24372

South Asian (SAS)

AF:

0.0000744

AC:

AN:

40324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2328

European-Non Finnish (NFE)

AF:

0.00000811

AC:

AN:

246514

Other (OTH)

AF:

0.00

AC:

AN:

21488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.20

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over