rs7217374

Positions:

• chr17-78146928-G-A
• chr17-78146928-G-C

Variant summary

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

The NM_001163075.2(C17orf99):​c.70+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,548,598 control chromosomes in the GnomAD database, including 161,476 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 0.45 (15865 hom., cov: 32)
  • Exomes 𝑓: 0.45 (145611 hom.)
• Consequence: C17orf99 NM_001163075.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C17orf99	NM_001163075.2	c.70+17G>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.70+17G>A		intron_variant		1	NM_001163075.2	ENSP00000343493	P1
C17orf99	ENST00000591995.1	c.58+17G>A		intron_variant		4		ENSP00000466133
C17orf99	ENST00000586999.2	n.73+17G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68327 AN: 151856 Hom.: 15841 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.475

GnomAD3 exomes AF: 0.424 AC: 65592 AN: 154790 Hom.: 14916 AF XY: 0.431 AC XY: 35325 AN XY: 82032

Gnomad AFR exome AF: 0.455

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.165

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.451 AC: 629588 AN: 1396624 Hom.: 145611 Cov.: 32 AF XY: 0.453 AC XY: 311752 AN XY: 688870

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.450 AC: 68403 AN: 151974 Hom.: 15865 Cov.: 32 AF XY: 0.448 AC XY: 33252 AN XY: 74280

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.479

Alfa AF: 0.469 Hom.: 22946

Bravo AF: 0.441

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.63

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: rs7217374; hg19: chr17-76143009; COSMIC: COSV59209541; COSMIC: COSV59209541;