rs61734132

chr7-138917686-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001164665.2(KIAA1549):c.1940C>G(p.Ser647Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 1,609,428 control chromosomes in the GnomAD database, including 3,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (286 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3577 hom.)
• Consequence: KIAA1549 NM_001164665.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.937

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020231009).
• BP6: Variant 7-138917686-G-C is Benign according to our data. Variant chr7-138917686-G-C is described in ClinVar as [Benign]. Clinvar id is 1167366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1549	NM_001164665.2	c.1940C>G	p.Ser647Cys	missense_variant	2/20	ENST00000422774.2
KIAA1549	NM_020910.3	c.1940C>G	p.Ser647Cys	missense_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1549	ENST00000422774.2	c.1940C>G	p.Ser647Cys	missense_variant	2/20	1	NM_001164665.2	A2
KIAA1549	ENST00000440172.5	c.1940C>G	p.Ser647Cys	missense_variant	2/20	1		P4

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8379 AN: 152128 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0631 AC: 15129 AN: 239650 Hom.: 612 AF XY: 0.0680 AC XY: 8835 AN XY: 129834

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.0329

Gnomad ASJ exome AF: 0.0778

Gnomad EAS exome AF: 0.000347

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0705

Gnomad OTH exome AF: 0.0708

GnomAD4 exome AF: 0.0663 AC: 96563 AN: 1457182 Hom.: 3577 Cov.: 49 AF XY: 0.0685 AC XY: 49613 AN XY: 724218

Gnomad4 AFR exome AF: 0.0352

Gnomad4 AMR exome AF: 0.0336

Gnomad4 ASJ exome AF: 0.0749

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0470

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0653

GnomAD4 genome AF: 0.0550 AC: 8378 AN: 152246 Hom.: 286 Cov.: 32 AF XY: 0.0552 AC XY: 4109 AN XY: 74436

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0455

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0680 Hom.: 99

Bravo AF: 0.0505

TwinsUK AF: 0.0739 AC: 274

ALSPAC AF: 0.0641 AC: 247

ESP6500AA AF: 0.0290 AC: 114

ESP6500EA AF: 0.0690 AC: 574

ExAC AF: 0.0649 AC: 7838

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Retinitis pigmentosa 86 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	18
Dann	Uncertain	0.98
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.031
Sift	Benign	0.059	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.99	D;D
Vest4		0.15
MPC		0.38
ClinPred		0.0072	T
GERP RS		1.1
Varity_R		0.054
gMVP		0.16

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: rs61734132; hg19: chr7-138602432; COSMIC: COSV54314336;