NM_015221.4:c.*592A>C

Variant names:

• chr10-99876559-T-G
• rs1139943
• NM_015221.4:c.*592A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015221.4(DNMBP):​c.*592A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,178 control chromosomes in the GnomAD database, including 1,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1958 hom., cov: 32)
  • Exomes 𝑓: 0.091 (0 hom.)
• Consequence: DNMBP NM_015221.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• Publications: 7 publications found

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP Gene-Disease associations (from GenCC):

• cataract 48

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	NM_015221.4	MANE Select	c.*592A>C		3_prime_UTR	Exon 17 of 17	NP_056036.1
	DNMBP	NR_199816.1		n.5544A>C		non_coding_transcript_exon	Exon 18 of 18
	DNMBP	NR_199817.1		n.3248A>C		non_coding_transcript_exon	Exon 15 of 15

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.*592A>C		3_prime_UTR	Exon 17 of 17	ENSP00000315659.4
	DNMBP	ENST00000543621.6	TSL:1	c.*592A>C		3_prime_UTR	Exon 14 of 14	ENSP00000443657.2
	DNMBP	ENST00000636706.1	TSL:2	c.*592A>C		3_prime_UTR	Exon 14 of 14	ENSP00000489875.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20031 AN: 152038 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0768

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.0909 AC: 2 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 1 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.132 AC: 20063 AN: 152156 Hom.: 1958 Cov.: 32 AF XY: 0.130 AC XY: 9633 AN XY: 74384

African (AFR) AF: 0.266 AC: 11039 AN: 41470

American (AMR) AF: 0.106 AC: 1617 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0768 AC: 266 AN: 3464

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5178

South Asian (SAS) AF: 0.115 AC: 553 AN: 4822

European-Finnish (FIN) AF: 0.0599 AC: 635 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68010

Other (OTH) AF: 0.130 AC: 274 AN: 2112

Alfa AF: 0.0961 Hom.: 1208

Bravo AF: 0.141

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.1
DANN	Benign	0.73
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs1139943; hg19: chr10-101636316;