rs10500127

chr7-138953680-C-Achr7-138953680-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001164665.2(KIAA1549):c.187+27403G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 152,188 control chromosomes in the GnomAD database, including 16 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 0.0099 (16 hom., cov: 33)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

KIAA1549 (HGNC:22219): (KIAA1549) The protein encoded by this gene belongs to the UPF0606 family. This gene has been found to be fused to the BRAF oncogene in many cases of pilocytic astrocytoma. The fusion results from 2Mb tandem duplications at 7q34. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.187+27403G>T		intron_variant		ENST00000422774.2
KIAA1549	NM_020910.3	c.187+27403G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.187+27403G>T		intron_variant		1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.187+27403G>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.00992 AC: 1508 AN: 152068 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.00991 AC: 1508 AN: 152188 Hom.: 16 Cov.: 33 AF XY: 0.00888 AC XY: 661 AN XY: 74418

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00312

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.0112

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.7
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: rs10500127; hg19: chr7-138638426;