7-44050264-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001014436.3(DBNL):c.123C>T(p.Arg41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,613,678 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (30 hom.)
• Consequence: DBNL NM_001014436.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.22

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005828202).
• BP6: Variant 7-44050264-C-T is Benign according to our data. Variant chr7-44050264-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.22 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBNL	NM_001014436.3	c.123C>T	p.Arg41=	synonymous_variant	2/13	ENST00000448521.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBNL	ENST00000448521.6	c.123C>T	p.Arg41=	synonymous_variant	2/13	1	NM_001014436.3	P4

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 664 AN: 152156 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00347 AC: 872 AN: 251450 Hom.: 3 AF XY: 0.00336 AC XY: 457 AN XY: 135900

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00883

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00467

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00528 AC: 7713 AN: 1461404 Hom.: 30 Cov.: 30 AF XY: 0.00509 AC XY: 3702 AN XY: 727022

Gnomad4 AFR exome AF: 0.00415

Gnomad4 AMR exome AF: 0.00423

Gnomad4 ASJ exome AF: 0.00911

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.00604

Gnomad4 OTH exome AF: 0.00494

GnomAD4 genome AF: 0.00436 AC: 664 AN: 152274 Hom.: 3 Cov.: 33 AF XY: 0.00441 AC XY: 328 AN XY: 74458

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.00772

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00522

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00542 Hom.: 2

Bravo AF: 0.00496

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.00558 AC: 48

ExAC AF: 0.00315 AC: 383

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DBNL: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.0
Dann	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;N
PROVEAN	Benign	1.6	N
REVEL	Benign	0.036
Sift	Benign	0.86	T
Vest4		0.23
MVP		0.067
ClinPred		0.0087	T
GERP RS		-2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs145680549; hg19: chr7-44089863; COSMIC: COSV68880866; COSMIC: COSV68880866;