rs6974263

chr7-138882364-A-Cchr7-138882364-A-Gchr7-138882364-A-T

Variant summary

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

The NM_001164665.2(KIAA1549):c.4033-780T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,184 control chromosomes in the GnomAD database, including 15,757 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 0.44 (15757 hom., cov: 33)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.4033-780T>G		intron_variant		ENST00000422774.2
KIAA1549	NM_020910.3	c.4033-780T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.4033-780T>G		intron_variant		1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.4033-780T>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67005 AN: 152066 Hom.: 15739 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.441 AC: 67057 AN: 152184 Hom.: 15757 Cov.: 33 AF XY: 0.435 AC XY: 32345 AN XY: 74392

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.471

Alfa AF: 0.395 Hom.: 21736

Bravo AF: 0.447

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.22
Dann	Benign	0.37

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: rs6974263; hg19: chr7-138567110;