17-9916961-T-C

Position:

• chr17-9916961-T-C

Variant summary

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

The NM_201433.2(GAS7):​c.*267A>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 0.438 in 527,204 control chromosomes in the GnomAD database, including 52,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14386 hom., cov: 33)
  • Exomes 𝑓: 0.44 (37700 hom.)
• Consequence: GAS7 NM_201433.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300

Genes affected

GAS7 (HGNC:4169): (growth arrest specific 7) Growth arrest-specific 7 is expressed primarily in terminally differentiated brain cells and predominantly in mature cerebellar Purkinje neurons. GAS7 plays a putative role in neuronal development. Several transcript variants encoding proteins which vary in the N-terminus have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-9916961-T-C is Benign according to our data. Variant chr17-9916961-T-C is described in ClinVar as [Benign]. Clinvar id is 1260702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS7	NM_201433.2	c.*267A>G		3_prime_UTR_variant	14/14	ENST00000432992.7	NP_958839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS7	ENST00000432992.7	c.*267A>G		3_prime_UTR_variant	14/14	1	NM_201433.2	ENSP00000407552.2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65456 AN: 151992 Hom.: 14371 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.422 AC: 21425 AN: 50712 Hom.: 4645 AF XY: 0.423 AC XY: 10830 AN XY: 25592

Gnomad AFR exome AF: 0.393

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.407

Gnomad SAS exome AF: 0.373

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.442 AC: 165618 AN: 375094 Hom.: 37700 Cov.: 0 AF XY: 0.441 AC XY: 85178 AN XY: 193116

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.431 AC: 65499 AN: 152110 Hom.: 14386 Cov.: 33 AF XY: 0.422 AC XY: 31402 AN XY: 74350

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.403

Alfa AF: 0.466 Hom.: 28526

Bravo AF: 0.426

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.9
DANN	Benign	0.74

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: rs2286532; hg19: chr17-9820278;