7-154052668-C-T

Variant names:

• chr7-154052668-C-T
• rs1974615
• NM_130797.4:c.-153C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130797.4(DPP6):​c.-153C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,219,902 control chromosomes in the GnomAD database, including 200,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (21948 hom., cov: 29)
  • Exomes 𝑓: 0.58 (178854 hom.)
• Consequence: DPP6 NM_130797.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.508
• Publications: 4 publications found

Genes affected

DPP6 (HGNC:3010): (dipeptidyl peptidase like 6) This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DPP6 Gene-Disease associations (from GenCC):

• autosomal dominant primary microcephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• paroxysmal familial ventricular fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal dominant 33

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000203335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-154052668-C-T is Benign according to our data. Variant chr7-154052668-C-T is described in ClinVar as Benign. ClinVar VariationId is 1183923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. 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
	DPP6	NM_130797.4	MANE Select	c.-153C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_130797.4	MANE Select	c.-153C>T		5_prime_UTR	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.-153C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001277182.1	Q8IYG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.-153C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.-153C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.-153C>T		5_prime_UTR	Exon 1 of 26	ENSP00000367001.3	P42658-1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 80355 AN: 149894 Hom.: 21933 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.575 AC: 615211 AN: 1069926 Hom.: 178854 Cov.: 32 AF XY: 0.577 AC XY: 298030 AN XY: 516330

African (AFR) AF: 0.403 AC: 8148 AN: 20226

American (AMR) AF: 0.603 AC: 7759 AN: 12870

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 5843 AN: 12002

East Asian (EAS) AF: 0.579 AC: 10285 AN: 17758

South Asian (SAS) AF: 0.652 AC: 32289 AN: 49534

European-Finnish (FIN) AF: 0.595 AC: 8789 AN: 14770

Middle Eastern (MID) AF: 0.480 AC: 1270 AN: 2646

European-Non Finnish (NFE) AF: 0.576 AC: 519120 AN: 900690

Other (OTH) AF: 0.551 AC: 21708 AN: 39430

GnomAD4 genome AF: 0.536 AC: 80413 AN: 149976 Hom.: 21948 Cov.: 29 AF XY: 0.543 AC XY: 39712 AN XY: 73082

African (AFR) AF: 0.419 AC: 17077 AN: 40758

American (AMR) AF: 0.600 AC: 9090 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1781 AN: 3456

East Asian (EAS) AF: 0.539 AC: 2656 AN: 4926

South Asian (SAS) AF: 0.648 AC: 3069 AN: 4738

European-Finnish (FIN) AF: 0.614 AC: 6185 AN: 10070

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 38934 AN: 67578

Other (OTH) AF: 0.522 AC: 1090 AN: 2090

Alfa AF: 0.547 Hom.: 2765

Bravo AF: 0.523

Asia WGS AF: 0.544 AC: 1886 AN: 3472

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	-0.53
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		-0.51
PromoterAI		-0.022	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1974615; hg19: chr7-153749753;