NM_001164665.2:c.5248-4136G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001164665.2(KIAA1549):​c.5248-4136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 151,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000079 (12/151818) while in subpopulation AFR AF = 0.000218 (9/41316). AF 95% confidence interval is 0.000113. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.5248-4136G>A		intron_variant	Intron 16 of 19	ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.5248-4136G>A		intron_variant	Intron 16 of 19		NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.5248-4136G>A		intron_variant	Intron 16 of 19	1	NM_001164665.2	ENSP00000416040.2
KIAA1549	ENST00000440172.5	c.5248-4136G>A		intron_variant	Intron 16 of 19	1		ENSP00000406661.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151818 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151818 Hom.: 0 Cov.: 31 AF XY: 0.0000810 AC XY: 6 AN XY: 74118

African (AFR) AF: 0.000218 AC: 9 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.96
PhyloP100		0.40

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;