rs2241039

Positions:

• chr16-90022029-G-A
• chr16-90022029-G-C

Variant summary

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

The NM_001286209.2(GAS8):​c.-73+2261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,938 control chromosomes in the GnomAD database, including 15,033 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 0.44 (15033 hom., cov: 32)
  • Exomes 𝑓: 0.29 (0 hom.)
• Consequence: GAS8 NM_001286209.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

GAS8 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS8	NM_001286209.2	c.-73+2261G>A		intron_variant			NP_001273138.1
GAS8	XM_011522992.3	c.-269+2261G>A		intron_variant			XP_011521294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000536122.7	c.-73+2261G>A		intron_variant		2		ENSP00000440977	A1
GAS8	ENST00000561675.1	c.-269+2261G>A		intron_variant		3		ENSP00000457554
GAS8	ENST00000563980.5	n.223-18G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66044 AN: 151804 Hom.: 15005 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.286 AC: 4 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.435 AC: 66126 AN: 151924 Hom.: 15033 Cov.: 32 AF XY: 0.449 AC XY: 33338 AN XY: 74262

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.444

Alfa AF: 0.396 Hom.: 8670

Bravo AF: 0.430

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2241039; hg19: chr16-90088437;