22-41288804-G-C

Variant names:

• chr22-41288804-G-C
• rs1003619
• NM_001317930.2:c.-38-7722C>G

Variant summary

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

The NM_001317930.2(RANGAP1):​c.-38-7722C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,776 control chromosomes in the GnomAD database, including 12,596 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 0.40 (12596 hom., cov: 30)
• Consequence: RANGAP1 NM_001317930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317930.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGAP1	NM_001317930.2		c.-38-7722C>G		intron	N/A	NP_001304859.1	P46060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60375 AN: 151658 Hom.: 12592 Cov.: 30

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.398 AC: 60391 AN: 151776 Hom.: 12596 Cov.: 30 AF XY: 0.393 AC XY: 29202 AN XY: 74214

African (AFR) AF: 0.345 AC: 14282 AN: 41342

American (AMR) AF: 0.283 AC: 4311 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3468

East Asian (EAS) AF: 0.182 AC: 942 AN: 5174

South Asian (SAS) AF: 0.352 AC: 1689 AN: 4798

European-Finnish (FIN) AF: 0.518 AC: 5463 AN: 10546

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30800 AN: 67926

Other (OTH) AF: 0.389 AC: 819 AN: 2106

Alfa AF: 0.325 Hom.: 971

Bravo AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		0.81

Splicing

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

Other links and lift over

dbSNP: rs1003619; hg19: chr22-41684808;