rs1993068

Variant names:

• chr7-138856405-C-A
• rs1993068
• NM_001164665.2:c.5248-4136G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-138856405-C-A
• chr7-138856405-C-G
• chr7-138856405-C-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.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
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 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.5248-4136G>T		intron	N/A	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.5248-4136G>T		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.5248-4136G>T		intron	N/A	ENSP00000416040.2	Q9HCM3-1
	KIAA1549	ENST00000440172.5	TSL:1	c.5248-4136G>T		intron	N/A	ENSP00000406661.1	Q9HCM3-2
	KIAA1549	ENST00000924635.1		c.4870-4136G>T		intron	N/A	ENSP00000594694.1

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

African (AFR) AF: 0.729 AC: 30183 AN: 41402

American (AMR) AF: 0.410 AC: 6256 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1859 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1641 AN: 4798

European-Finnish (FIN) AF: 0.404 AC: 4255 AN: 10524

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23295 AN: 67948

Other (OTH) AF: 0.399 AC: 837 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.83
PhyloP100		0.40
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: rs1993068; hg19: chr7-138541151;