rs11656744

chr17-78147353-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.70+442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,188 control chromosomes in the GnomAD database, including 1,849 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 0.15 (1849 hom., cov: 32)
• Consequence: C17orf99 NM_001163075.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C17orf99	NM_001163075.2	c.70+442G>A		intron_variant		ENST00000340363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C17orf99	ENST00000340363.10	c.70+442G>A		intron_variant		1	NM_001163075.2	P1
C17orf99	ENST00000591995.1	c.58+442G>A		intron_variant		4
C17orf99	ENST00000586999.2	n.73+442G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22977 AN: 152070 Hom.: 1842 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.151 AC: 23029 AN: 152188 Hom.: 1849 Cov.: 32 AF XY: 0.155 AC XY: 11541 AN XY: 74414

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.177

Alfa AF: 0.158 Hom.: 2540

Bravo AF: 0.144

Asia WGS AF: 0.190 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.9
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11656744; hg19: chr17-76143434;