rs145680549

Variant names:

• chr7-44050264-C-T
• rs145680549
• NM_001014436.3:c.123C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001284315.2(DBNL):​c.26C>T​(p.Ala9Val) variant causes a missense 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. 14/18 in silico tools predict 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_001284315.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.22
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -10 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 VariationId is 2657417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284315.2. 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
	DBNL	NM_001014436.3	MANE Select	c.123C>T	p.Arg41Arg	synonymous	Exon 2 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001284315.2		c.26C>T	p.Ala9Val	missense	Exon 2 of 11	NP_001271244.1	Q9UJU6-4
	DBNL	NM_001122956.2		c.123C>T	p.Arg41Arg	synonymous	Exon 2 of 13	NP_001116428.1	Q9UJU6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.123C>T	p.Arg41Arg	synonymous	Exon 2 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000494774.5	TSL:1	c.123C>T	p.Arg41Arg	synonymous	Exon 2 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000497184.5	TSL:1	n.381C>T		non_coding_transcript_exon	Exon 1 of 10

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

GnomAD2 exomes AF: 0.00347 AC: 872 AN: 251450 AF XY: 0.00336

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 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

African (AFR) AF: 0.00415 AC: 139 AN: 33462

American (AMR) AF: 0.00423 AC: 189 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00911 AC: 238 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00110 AC: 95 AN: 86252

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53366

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.00604 AC: 6720 AN: 1111684

Other (OTH) AF: 0.00494 AC: 298 AN: 60372

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

African (AFR) AF: 0.00339 AC: 141 AN: 41560

American (AMR) AF: 0.00772 AC: 118 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00522 AC: 355 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00502 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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
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
PhyloP100		-3.2
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
PromoterAI		0.044	Neutral
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

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