rs1993068

Positions:

• chr7-138856405-C-A
• chr7-138856405-C-G
• chr7-138856405-C-T

Variant summary

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

The NM_001164665.2(KIAA1549):​c.5248-4136G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,844 control chromosomes in the GnomAD database, including 18,327 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 0.46 (18327 hom., cov: 31)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.5248-4136G>T		intron_variant		ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.5248-4136G>T		intron_variant			NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.5248-4136G>T		intron_variant		1	NM_001164665.2	ENSP00000416040.2
KIAA1549	ENST00000440172.5	c.5248-4136G>T		intron_variant		1		ENSP00000406661.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69571 AN: 151726 Hom.: 18283 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.459 AC: 69667 AN: 151844 Hom.: 18327 Cov.: 31 AF XY: 0.457 AC XY: 33931 AN XY: 74190

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.399

Alfa AF: 0.248 Hom.: 530

Bravo AF: 0.470

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.83

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: rs1993068; hg19: chr7-138541151; COSMIC: COSV99649634;