rs11656744

Variant names:

• chr17-78147353-G-A
• rs11656744
• NM_001163075.2:c.70+442G>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.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
• Publications: 12 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=-0.8).
• 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 rank	MANE	Protein	UniProt
C17orf99	NM_001163075.2	c.70+442G>A		intron_variant	Intron 2 of 4	ENST00000340363.10	NP_001156547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C17orf99	ENST00000340363.10	c.70+442G>A		intron_variant	Intron 2 of 4	1	NM_001163075.2	ENSP00000343493.4
C17orf99	ENST00000591995.1	c.58+442G>A		intron_variant	Intron 1 of 2	4		ENSP00000466133.1
C17orf99	ENST00000586999.2	n.73+442G>A		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.125 AC: 5184 AN: 41528

American (AMR) AF: 0.142 AC: 2169 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.133 AC: 689 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1118 AN: 4832

European-Finnish (FIN) AF: 0.201 AC: 2136 AN: 10606

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10248 AN: 67968

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.155 Hom.: 3401

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
PhyloP100		0.91
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11656744; hg19: chr17-76143434;