chr22-41265150-G-T

Variant names:

• chr22-41265150-G-T
• rs2235852
• NM_002883.4:c.301-307C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002883.4(RANGAP1):​c.301-307C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,036 control chromosomes in the GnomAD database, including 8,878 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 0.33 (8878 hom., cov: 32)
• Consequence: RANGAP1 NM_002883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 21 publications found

Genes affected

RANGAP1 (HGNC:9854): (Ran GTPase activating protein 1) This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002883.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGAP1	NM_002883.4	MANE Select	c.301-307C>A		intron	N/A	NP_002874.1
	RANGAP1	NM_001278651.2		c.301-307C>A		intron	N/A	NP_001265580.1
	RANGAP1	NM_001317930.2		c.301-307C>A		intron	N/A	NP_001304859.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGAP1	ENST00000356244.8	TSL:1 MANE Select	c.301-307C>A		intron	N/A	ENSP00000348577.3
	RANGAP1	ENST00000405486.5	TSL:1	c.301-307C>A		intron	N/A	ENSP00000385866.1
	RANGAP1	ENST00000455915.6	TSL:1	c.301-307C>A		intron	N/A	ENSP00000401470.2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50072 AN: 151918 Hom.: 8860 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.330 AC: 50119 AN: 152036 Hom.: 8878 Cov.: 32 AF XY: 0.337 AC XY: 25062 AN XY: 74306

African (AFR) AF: 0.242 AC: 10059 AN: 41490

American (AMR) AF: 0.514 AC: 7849 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2627 AN: 5152

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4816

European-Finnish (FIN) AF: 0.330 AC: 3486 AN: 10568

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21650 AN: 67970

Other (OTH) AF: 0.350 AC: 736 AN: 2102

Alfa AF: 0.325 Hom.: 35223

Bravo AF: 0.344

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.039
DANN	Benign	0.42
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2235852; hg19: chr22-41661154;