Genetic Variant KIAA1549:c.5248-4136G>A (chr7-138856405-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

Publications

2 publications found

Variant links:

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

KIAA1549 links:

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ACMG classification

Classification was made for transcript

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.

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>A		intron	N/A	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.5248-4136G>A		intron	N/A	NP_065961.2	Q9HCM3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIAA1549	ENST00000422774.2	TSL:1 MANE Select	c.5248-4136G>A	intron	N/A	ENSP00000416040.2	Q9HCM3-1
KIAA1549	ENST00000440172.5	TSL:1	c.5248-4136G>A	intron	N/A	ENSP00000406661.1	Q9HCM3-2
KIAA1549	ENST00000924635.1		c.4870-4136G>A	intron	N/A	ENSP00000594694.1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151818

Hom.:

Cov.:

show subpopulations

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:

AN:

151818

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41316

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.7

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over