rs748708

Variant names:

• chr17-78146714-G-A
• rs748708
• NM_001163075.2:c.38-165G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C17orf99	NM_001163075.2	c.38-165G>A		intron_variant	Intron 1 of 4	ENST00000340363.10	NP_001156547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C17orf99	ENST00000340363.10	c.38-165G>A		intron_variant	Intron 1 of 4	1	NM_001163075.2	ENSP00000343493.4
C17orf99	ENST00000586999.2	n.41-165G>A		intron_variant	Intron 1 of 2	2
C17orf99	ENST00000591995.1	c.-140G>A		upstream_gene_variant		4		ENSP00000466133.1

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

African (AFR) AF: 0.105 AC: 1557 AN: 14880

American (AMR) AF: 0.0949 AC: 2400 AN: 25294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 2865 AN: 15386

East Asian (EAS) AF: 0.113 AC: 3537 AN: 31412

South Asian (SAS) AF: 0.133 AC: 6769 AN: 50716

European-Finnish (FIN) AF: 0.166 AC: 7050 AN: 42352

Middle Eastern (MID) AF: 0.177 AC: 577 AN: 3252

European-Non Finnish (NFE) AF: 0.115 AC: 38974 AN: 340236

Other (OTH) AF: 0.122 AC: 3584 AN: 29372

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

African (AFR) AF: 0.103 AC: 4228 AN: 41228

American (AMR) AF: 0.116 AC: 1688 AN: 14502

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 628 AN: 3120

East Asian (EAS) AF: 0.124 AC: 639 AN: 5148

South Asian (SAS) AF: 0.144 AC: 655 AN: 4544

European-Finnish (FIN) AF: 0.197 AC: 1915 AN: 9712

Middle Eastern (MID) AF: 0.231 AC: 61 AN: 264

European-Non Finnish (NFE) AF: 0.127 AC: 7807 AN: 61530

Other (OTH) AF: 0.151 AC: 298 AN: 1972

Alfa AF: 0.119 Hom.: 1469

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
PhyloP100		0.43
PromoterAI		-0.047	Neutral
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: rs748708; hg19: chr17-76142795;