17-9969451-A-G

Position:

• chr17-9969451-A-G

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.471+226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,070 control chromosomes in the GnomAD database, including 49,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.80 (49305 hom., cov: 30)
• Consequence: GAS7 NM_201433.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.02

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=-0.9).
• BP6: Variant 17-9969451-A-G is Benign according to our data. Variant chr17-9969451-A-G is described in ClinVar as [Benign]. Clinvar id is 1255118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS7	NM_201433.2	c.471+226T>C		intron_variant		ENST00000432992.7	NP_958839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS7	ENST00000432992.7	c.471+226T>C		intron_variant		1	NM_201433.2	ENSP00000407552	P1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121475 AN: 151952 Hom.: 49251 Cov.: 30

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.794

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 121594 AN: 152070 Hom.: 49305 Cov.: 30 AF XY: 0.800 AC XY: 59439 AN XY: 74308

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.796

Alfa AF: 0.758 Hom.: 60091

Bravo AF: 0.809

Asia WGS AF: 0.757 AC: 2633 AN: 3476

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.55

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: rs2277689; hg19: chr17-9872768; COSMIC: COSV60433378;