chr6-109071788-C-T

Variant names:

• chr6-109071788-C-T
• rs17070142
• NM_014454.3:c.279+22007G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014454.3(SESN1):​c.279+22007G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 152,232 control chromosomes in the GnomAD database, including 336 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 0.047 (336 hom., cov: 32)
• Consequence: SESN1 NM_014454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 3 publications found

Genes affected

SESN1 (HGNC:21595): (sestrin 1) This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SESN1	NM_014454.3	c.279+22007G>A		intron_variant	Intron 1 of 9	ENST00000436639.7	NP_055269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SESN1	ENST00000436639.7	c.279+22007G>A		intron_variant	Intron 1 of 9	1	NM_014454.3	ENSP00000393762.2

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7090 AN: 152114 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0467 AC: 7109 AN: 152232 Hom.: 336 Cov.: 32 AF XY: 0.0450 AC XY: 3350 AN XY: 74446

African (AFR) AF: 0.120 AC: 4989 AN: 41512

American (AMR) AF: 0.0268 AC: 410 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3468

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5178

South Asian (SAS) AF: 0.0288 AC: 139 AN: 4826

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1211 AN: 68016

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0356 Hom.: 251

Bravo AF: 0.0513

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.65
PhyloP100		-0.52
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: rs17070142; hg19: chr6-109392991;