rs10435435

chr7-138835766-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164665.2(KIAA1549):c.*2140A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 220,240 control chromosomes in the GnomAD database, including 2,556 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 0.12 (1382 hom., cov: 32)
  • Exomes 𝑓: 0.17 (1174 hom.)
• Consequence: KIAA1549 NM_001164665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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]

TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.*2140A>G		3_prime_UTR_variant	20/20	ENST00000422774.2
KIAA1549	NM_020910.3	c.*2140A>G		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.*2140A>G		3_prime_UTR_variant	20/20	1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.*2140A>G		3_prime_UTR_variant	20/20	1		P4
TMEM213	ENST00000413208.1	c.155-2103T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18175 AN: 152080 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.170 AC: 11572 AN: 68042 Hom.: 1174 Cov.: 0 AF XY: 0.171 AC XY: 5391 AN XY: 31556

Gnomad4 AFR exome AF: 0.0408

Gnomad4 AMR exome AF: 0.0963

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.119 AC: 18178 AN: 152198 Hom.: 1382 Cov.: 32 AF XY: 0.121 AC XY: 8984 AN XY: 74418

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.141

Alfa AF: 0.135 Hom.: 495

Bravo AF: 0.114

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.39

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

LitVar

Other links and lift over

dbSNP: rs10435435; hg19: chr7-138520511;