chr7-138833311-C-T

Position:

• chr7-138833311-C-T

Variant summary

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

The NM_001164665.2(KIAA1549):​c.*4595G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 232,280 control chromosomes in the GnomAD database, including 72,311 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 0.79 (48117 hom., cov: 33)
  • Exomes 𝑓: 0.77 (24194 hom.)
• Consequence: KIAA1549 NM_001164665.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.914

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549	NM_001164665.2	c.*4595G>A		3_prime_UTR_variant	20/20	ENST00000422774.2	NP_001158137.1
KIAA1549	NM_020910.3	c.*4595G>A		3_prime_UTR_variant	20/20		NP_065961.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1549	ENST00000422774.2	c.*4595G>A		3_prime_UTR_variant	20/20	1	NM_001164665.2	ENSP00000416040	A2
KIAA1549	ENST00000440172.5	c.*4595G>A		3_prime_UTR_variant	20/20	1		ENSP00000406661	P4
TMEM213	ENST00000413208.1	c.155-4558C>T		intron_variant		3		ENSP00000401570

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119629 AN: 152064 Hom.: 48051 Cov.: 33

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.797

GnomAD4 exome AF: 0.773 AC: 61899 AN: 80098 Hom.: 24194 Cov.: 0 AF XY: 0.772 AC XY: 28481 AN XY: 36878

Gnomad4 AFR exome AF: 0.953

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.773

Gnomad4 EAS exome AF: 0.954

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.723

Gnomad4 OTH exome AF: 0.763

GnomAD4 genome AF: 0.787 AC: 119756 AN: 152182 Hom.: 48117 Cov.: 33 AF XY: 0.782 AC XY: 58155 AN XY: 74378

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.799

Alfa AF: 0.735 Hom.: 54227

Bravo AF: 0.805

Asia WGS AF: 0.826 AC: 2872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.71

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: rs896193; hg19: chr7-138518056;