chr17-9918157-C-T

Variant names:

• chr17-9918157-C-T
• rs2270122
• NM_201433.2:c.1219-58G>A

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.1219-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,253,650 control chromosomes in the GnomAD database, including 16,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4167 hom., cov: 33)
  • Exomes 𝑓: 0.14 (12628 hom.)
• Consequence: GAS7 NM_201433.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12
• Publications: 5 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 17-9918157-C-T is Benign according to our data. Variant chr17-9918157-C-T is described in ClinVar as Benign. ClinVar VariationId is 1228161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS7	NM_201433.2	MANE Select	c.1219-58G>A		intron	N/A	NP_958839.1	O60861-3
	GAS7	NM_201432.2		c.1039-58G>A		intron	N/A	NP_958836.1	O60861-4
	GAS7	NM_001130831.2		c.1027-58G>A		intron	N/A	NP_001124303.1	O60861-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS7	ENST00000432992.7	TSL:1 MANE Select	c.1219-58G>A		intron	N/A	ENSP00000407552.2	O60861-3
	GAS7	ENST00000323816.8	TSL:1	c.1039-58G>A		intron	N/A	ENSP00000322608.5	O60861-4
	GAS7	ENST00000585266.5	TSL:1	c.1039-58G>A		intron	N/A	ENSP00000464240.2	O60861-4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31591 AN: 151940 Hom.: 4157 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.137 AC: 150624 AN: 1101594 Hom.: 12628 AF XY: 0.138 AC XY: 77332 AN XY: 561200

African (AFR) AF: 0.363 AC: 9298 AN: 25590

American (AMR) AF: 0.248 AC: 9824 AN: 39684

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3595 AN: 22952

East Asian (EAS) AF: 0.303 AC: 11356 AN: 37474

South Asian (SAS) AF: 0.196 AC: 15013 AN: 76700

European-Finnish (FIN) AF: 0.192 AC: 9018 AN: 46928

Middle Eastern (MID) AF: 0.174 AC: 874 AN: 5014

European-Non Finnish (NFE) AF: 0.105 AC: 83988 AN: 798822

Other (OTH) AF: 0.158 AC: 7658 AN: 48430

GnomAD4 genome AF: 0.208 AC: 31645 AN: 152056 Hom.: 4167 Cov.: 33 AF XY: 0.211 AC XY: 15683 AN XY: 74322

African (AFR) AF: 0.364 AC: 15082 AN: 41442

American (AMR) AF: 0.213 AC: 3253 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1444 AN: 5156

South Asian (SAS) AF: 0.205 AC: 984 AN: 4798

European-Finnish (FIN) AF: 0.206 AC: 2177 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7644 AN: 67996

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.169 Hom.: 360

Bravo AF: 0.218

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.78
PhyloP100		-1.1
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: rs2270122; hg19: chr17-9821474; COSMIC: COSV60437971;