rs6974263

Variant names:

• chr7-138882364-A-C
• rs6974263
• NM_001164665.2:c.4033-780T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-138882364-A-C
• chr7-138882364-A-G
• chr7-138882364-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

KIAA1549 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 86

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164665.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549	NM_001164665.2	MANE Select	c.4033-780T>G		intron	N/A	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.4033-780T>G		intron	N/A	NP_065961.2	Q9HCM3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549	ENST00000422774.2	TSL:1 MANE Select	c.4033-780T>G		intron	N/A	ENSP00000416040.2	Q9HCM3-1
	KIAA1549	ENST00000440172.5	TSL:1	c.4033-780T>G		intron	N/A	ENSP00000406661.1	Q9HCM3-2
	KIAA1549	ENST00000924635.1		c.4033-780T>G		intron	N/A	ENSP00000594694.1

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

African (AFR) AF: 0.600 AC: 24908 AN: 41526

American (AMR) AF: 0.317 AC: 4853 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1699 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5166

South Asian (SAS) AF: 0.428 AC: 2064 AN: 4824

European-Finnish (FIN) AF: 0.337 AC: 3567 AN: 10586

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26812 AN: 67992

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.409 Hom.: 33119

Bravo AF: 0.447

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-1.2
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: rs6974263; hg19: chr7-138567110;