20-49017469-AT-ATTT

Variant names:

• chr20-49017469-A-ATT
• rs11086275
• NM_006420.3:c.4455-20_4455-19dupTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_006420.3(ARFGEF2):​c.4455-20_4455-19dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,422 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: 𝑓 0.0000066 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ARFGEF2 NM_006420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

Genes affected

ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000288 (42/1459768) while in subpopulation AMR AF= 0.0000896 (4/44652). AF 95% confidence interval is 0.0000299. There are 0 homozygotes in gnomad4_exome. There are 15 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFGEF2	NM_006420.3	c.4455-20_4455-19dupTT		intron_variant	Intron 32 of 38	ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1	c.4452-20_4452-19dupTT		intron_variant	Intron 32 of 38		NP_001397775.1
ARFGEF2	XM_047439832.1	c.3891-20_3891-19dupTT		intron_variant	Intron 30 of 36		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.4455-27_4455-26insTT		intron_variant	Intron 32 of 38	1	NM_006420.3	ENSP00000360985.4

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151654 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1459768 Hom.: 0 Cov.: 33 AF XY: 0.0000207 AC XY: 15 AN XY: 726178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000896

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151654 Hom.: 0 Cov.: 25 AF XY: 0.0000135 AC XY: 1 AN XY: 74014

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11086275; hg19: chr20-47634006;