chr7-44058434-C-T

Variant names:

• chr7-44058434-C-T
• rs147233974
• ENST00000494774.5:c.710C>T

Variant summary

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

The NM_001014436.3(DBNL):​c.707C>T​(p.Thr236Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,614,198 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (12 hom.)
• Consequence: DBNL NM_001014436.3 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.39
• Publications: 10 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=0.0039149225).
• BP6: Variant 7-44058434-C-T is Benign according to our data. Variant chr7-44058434-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014436.3. 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.707C>T	p.Thr236Met	missense splice_region	Exon 8 of 13	NP_001014436.1	Q9UJU6-1
	DBNL	NM_001122956.2		c.710C>T	p.Thr237Met	missense	Exon 8 of 13	NP_001116428.1	Q9UJU6-3
	DBNL	NM_014063.7		c.710C>T	p.Thr237Met	missense	Exon 8 of 13	NP_054782.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBNL	ENST00000494774.5	TSL:1	c.710C>T	p.Thr237Met	missense	Exon 8 of 13	ENSP00000419992.1	Q9UJU6-2
	DBNL	ENST00000448521.6	TSL:1 MANE Select	c.707C>T	p.Thr236Met	missense splice_region	Exon 8 of 13	ENSP00000411701.1	Q9UJU6-1
	DBNL	ENST00000497184.5	TSL:1	n.2783C>T		splice_region non_coding_transcript_exon	Exon 5 of 10

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 302 AN: 152224 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00242 AC: 608 AN: 250778 AF XY: 0.00254

Gnomad AFR exome AF: 0.000555

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00314

Gnomad OTH exome AF: 0.00654

GnomAD4 exome AF: 0.00226 AC: 3307 AN: 1461856 Hom.: 12 Cov.: 34 AF XY: 0.00233 AC XY: 1693 AN XY: 727226

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.00418 AC: 187 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 61 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00151 AC: 130 AN: 86254

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53408

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5768

European-Non Finnish (NFE) AF: 0.00235 AC: 2612 AN: 1111996

Other (OTH) AF: 0.00293 AC: 177 AN: 60394

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152342 Hom.: 5 Cov.: 33 AF XY: 0.00211 AC XY: 157 AN XY: 74502

African (AFR) AF: 0.000457 AC: 19 AN: 41576

American (AMR) AF: 0.00444 AC: 68 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00257 AC: 175 AN: 68026

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00292 Hom.: 2

Bravo AF: 0.00254

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00244 AC: 21

ExAC AF: 0.00245 AC: 297

Asia WGS AF: 0.000866 AC: 4 AN: 3478

EpiCase AF: 0.00507

EpiControl AF: 0.00474

ClinVar

ClinVar submissions

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	0.078
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.067
Sift	Benign	0.077	T
Sift4G	Benign	0.10	T
Polyphen		0.97	D
Vest4		0.14
MVP		0.73
MPC		0.28
ClinPred		0.026	T
GERP RS		2.1
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.11
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs147233974; hg19: chr7-44098033;