rs10500127

Variant names:

• chr7-138953680-C-A
• rs10500127
• NM_001164665.2:c.187+27403G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-138953680-C-A
• chr7-138953680-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001164665.2(KIAA1549):​c.187+27403G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00991 in 152,188 control chromosomes in the GnomAD database, including 16 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 0.0099 (16 hom., cov: 33)
• Consequence: KIAA1549 NM_001164665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 0 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00991 (1508/152188) while in subpopulation NFE AF = 0.0152 (1036/68000). AF 95% confidence interval is 0.0145. There are 16 homozygotes in GnomAd4. There are 661 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

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.187+27403G>T		intron	N/A	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.187+27403G>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.187+27403G>T		intron	N/A	ENSP00000416040.2	Q9HCM3-1
	KIAA1549	ENST00000440172.5	TSL:1	c.187+27403G>T		intron	N/A	ENSP00000406661.1	Q9HCM3-2
	KIAA1549	ENST00000924635.1		c.187+27403G>T		intron	N/A	ENSP00000594694.1

Frequencies

GnomAD3 genomes AF: 0.00992 AC: 1508 AN: 152068 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.00991 AC: 1508 AN: 152188 Hom.: 16 Cov.: 33 AF XY: 0.00888 AC XY: 661 AN XY: 74418

African (AFR) AF: 0.00306 AC: 127 AN: 41528

American (AMR) AF: 0.0141 AC: 215 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4828

European-Finnish (FIN) AF: 0.00312 AC: 33 AN: 10582

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1036 AN: 68000

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.0112

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10500127;

hg19: chr7-138638426;