17-9969451-A-G

Variant names:

• chr17-9969451-A-G
• rs2277689
• NM_201433.2:c.471+226T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201433.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS7	NM_201433.2	MANE Select	c.471+226T>C		intron	N/A	NP_958839.1
	GAS7	NM_201432.2		c.291+226T>C		intron	N/A	NP_958836.1
	GAS7	NM_001130831.2		c.279+226T>C		intron	N/A	NP_001124303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS7	ENST00000432992.7	TSL:1 MANE Select	c.471+226T>C		intron	N/A	ENSP00000407552.2
	GAS7	ENST00000323816.8	TSL:1	c.291+226T>C		intron	N/A	ENSP00000322608.5
	GAS7	ENST00000585266.5	TSL:1	c.291+226T>C		intron	N/A	ENSP00000464240.2

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

African (AFR) AF: 0.938 AC: 38932 AN: 41512

American (AMR) AF: 0.770 AC: 11761 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3459 AN: 5156

South Asian (SAS) AF: 0.758 AC: 3652 AN: 4820

European-Finnish (FIN) AF: 0.776 AC: 8197 AN: 10560

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49943 AN: 67954

Other (OTH) AF: 0.796 AC: 1682 AN: 2112

Alfa AF: 0.763 Hom.: 84126

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

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.55
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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