chr7-138837987-C-G

Variant names:

• chr7-138837987-C-G
• rs748810208
• NM_001164665.2:c.5772G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001164665.2(KIAA1549):​c.5772G>C​(p.Ser1924Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,016 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. Synonymous variant affecting the same amino acid position (i.e. S1924S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA1549 NM_001164665.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-4.02 with no splicing effect.

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.5772G>C	p.Ser1924Ser	synonymous	Exon 20 of 20	NP_001158137.1	Q9HCM3-1
	KIAA1549	NM_020910.3		c.5724G>C	p.Ser1908Ser	synonymous	Exon 20 of 20	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.5772G>C	p.Ser1924Ser	synonymous	Exon 20 of 20	ENSP00000416040.2	Q9HCM3-1
	KIAA1549	ENST00000440172.5	TSL:1	c.5724G>C	p.Ser1908Ser	synonymous	Exon 20 of 20	ENSP00000406661.1	Q9HCM3-2
	KIAA1549	ENST00000924635.1		c.5346G>C	p.Ser1782Ser	synonymous	Exon 18 of 18	ENSP00000594694.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461016 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726648

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.38
DANN	Benign	0.68
PhyloP100		-4.0

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

Other links and lift over

dbSNP: rs748810208; hg19: chr7-138522732;