chr11-6621604-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003737.4(DCHS1):​c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 766,734 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 32)
Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

DCHS1
NM_003737.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.633
Variant links:
Genes affected
DCHS1 (HGNC:13681): (dachsous cadherin-related 1) This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008]
DCHS1-AS1 (HGNC:40650): (DCHS1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 11-6621604-C-T is Benign according to our data. Variant chr11-6621604-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0103 (1564/152320) while in subpopulation SAS AF= 0.0512 (247/4828). AF 95% confidence interval is 0.0459. There are 13 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DCHS1NM_003737.4 linkuse as main transcriptc.*175G>A 3_prime_UTR_variant 21/21 ENST00000299441.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DCHS1ENST00000299441.5 linkuse as main transcriptc.*175G>A 3_prime_UTR_variant 21/211 NM_003737.4 P1
DCHS1-AS1ENST00000526456.1 linkuse as main transcriptn.154C>T non_coding_transcript_exon_variant 1/24

Frequencies

GnomAD3 genomes
AF:
0.0103
AC:
1563
AN:
152202
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0142
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00739
Gnomad ASJ
AF:
0.00547
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.0511
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.00808
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.0130
AC:
1769
AN:
135998
Hom.:
28
AF XY:
0.0153
AC XY:
1126
AN XY:
73770
show subpopulations
Gnomad AFR exome
AF:
0.0127
Gnomad AMR exome
AF:
0.00488
Gnomad ASJ exome
AF:
0.00799
Gnomad EAS exome
AF:
0.000567
Gnomad SAS exome
AF:
0.0447
Gnomad FIN exome
AF:
0.00185
Gnomad NFE exome
AF:
0.00815
Gnomad OTH exome
AF:
0.0102
GnomAD4 exome
AF:
0.0114
AC:
7009
AN:
614414
Hom.:
121
Cov.:
8
AF XY:
0.0133
AC XY:
4358
AN XY:
328436
show subpopulations
Gnomad4 AFR exome
AF:
0.0148
Gnomad4 AMR exome
AF:
0.00559
Gnomad4 ASJ exome
AF:
0.00624
Gnomad4 EAS exome
AF:
0.000248
Gnomad4 SAS exome
AF:
0.0462
Gnomad4 FIN exome
AF:
0.00177
Gnomad4 NFE exome
AF:
0.00821
Gnomad4 OTH exome
AF:
0.0100
GnomAD4 genome
AF:
0.0103
AC:
1564
AN:
152320
Hom.:
13
Cov.:
32
AF XY:
0.0107
AC XY:
800
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0141
Gnomad4 AMR
AF:
0.00738
Gnomad4 ASJ
AF:
0.00547
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.0512
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00810
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00848
Hom.:
2
Bravo
AF:
0.00994
Asia WGS
AF:
0.0270
AC:
94
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 14, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
9.8
DANN
Benign
0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77307773; hg19: chr11-6642835; API