5-172770578-G-C

Variant names:

• chr5-172770578-G-C
• rs34507926
• NM_004417.4:c.367+8C>G

Variant summary

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

The NM_004417.4(DUSP1):​c.367+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,397,880 control chromosomes in the GnomAD database, including 3,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (496 hom., cov: 33)
  • Exomes 𝑓: 0.058 (3343 hom.)
• Consequence: DUSP1 NM_004417.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001416
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 10 publications found

Genes affected

DUSP1 (HGNC:3064): (dual specificity phosphatase 1) The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy. [provided by RefSeq, Aug 2017]

ENSG00000253736 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004417.4. 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
	DUSP1	NM_004417.4	MANE Select	c.367+8C>G		splice_region intron	N/A	NP_004408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP1	ENST00000239223.4	TSL:1 MANE Select	c.367+8C>G		splice_region intron	N/A	ENSP00000239223.3
	ENSG00000253736	ENST00000523005.1	TSL:3	n.70-6914G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8981 AN: 152064 Hom.: 492 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0695

GnomAD2 exomes AF: 0.0822 AC: 7151 AN: 86944 AF XY: 0.0790

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.0574

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.0438

Gnomad NFE exome AF: 0.0490

Gnomad OTH exome AF: 0.0651

GnomAD4 exome AF: 0.0575 AC: 71676 AN: 1245704 Hom.: 3343 Cov.: 31 AF XY: 0.0582 AC XY: 35216 AN XY: 605554

African (AFR) AF: 0.0242 AC: 610 AN: 25212

American (AMR) AF: 0.138 AC: 2389 AN: 17354

Ashkenazi Jewish (ASJ) AF: 0.0575 AC: 998 AN: 17348

East Asian (EAS) AF: 0.304 AC: 9304 AN: 30624

South Asian (SAS) AF: 0.107 AC: 5497 AN: 51504

European-Finnish (FIN) AF: 0.0408 AC: 1311 AN: 32156

Middle Eastern (MID) AF: 0.0864 AC: 293 AN: 3392

European-Non Finnish (NFE) AF: 0.0469 AC: 47670 AN: 1017108

Other (OTH) AF: 0.0707 AC: 3604 AN: 51006

GnomAD4 genome AF: 0.0591 AC: 9000 AN: 152176 Hom.: 496 Cov.: 33 AF XY: 0.0623 AC XY: 4638 AN XY: 74400

African (AFR) AF: 0.0270 AC: 1121 AN: 41556

American (AMR) AF: 0.109 AC: 1666 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1505 AN: 5150

South Asian (SAS) AF: 0.111 AC: 534 AN: 4826

European-Finnish (FIN) AF: 0.0491 AC: 520 AN: 10596

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0482 AC: 3277 AN: 67966

Other (OTH) AF: 0.0745 AC: 157 AN: 2108

Alfa AF: 0.0197 Hom.: 8

Bravo AF: 0.0649

Asia WGS AF: 0.195 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.90
PhyloP100		-1.5
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0
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: rs34507926; hg19: chr5-172197581; COSMIC: COSV53320771;