rs748708

Positions:

• chr17-78146714-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163075.2(C17orf99):​c.38-165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 695,788 control chromosomes in the GnomAD database, including 5,590 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 0.13 (1140 hom., cov: 31)
  • Exomes 𝑓: 0.12 (4450 hom.)
• Consequence: C17orf99 NM_001163075.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

Genes affected

C17orf99 (HGNC:34490): (chromosome 17 open reading frame 99) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; mature B cell differentiation involved in immune response; and positive regulation of immunoglobulin production in mucosal tissue. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C17orf99	NM_001163075.2	c.38-165G>A		intron_variant		ENST00000340363.10	NP_001156547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C17orf99	ENST00000340363.10	c.38-165G>A		intron_variant		1	NM_001163075.2	ENSP00000343493	P1
C17orf99	ENST00000586999.2	n.41-165G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 18106 AN: 142768 Hom.: 1136 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.122 AC: 67313 AN: 552900 Hom.: 4450 AF XY: 0.124 AC XY: 35410 AN XY: 286582

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0949

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.127 AC: 18137 AN: 142888 Hom.: 1140 Cov.: 31 AF XY: 0.130 AC XY: 9086 AN XY: 69862

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.151

Alfa AF: 0.122 Hom.: 1005

Bravo AF: 0.114

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs748708; hg19: chr17-76142795;