NM_015221.4:c.*10G>C

Variant names:

• chr10-99877141-C-G
• rs2256287
• NM_015221.4:c.*10G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_015221.4(DNMBP):​c.*10G>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 0.00201 in 1,597,454 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: DNMBP NM_015221.4 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.213
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-99877141-C-G is Benign according to our data. Variant chr10-99877141-C-G is described in ClinVar as Benign. ClinVar VariationId is 3038451.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1554/152198) while in subpopulation AFR AF = 0.0352 (1460/41510). AF 95% confidence interval is 0.0337. There are 33 homozygotes in GnomAd4. There are 741 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	NM_015221.4	MANE Select	c.*10G>C		3_prime_UTR	Exon 17 of 17	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001441287.1		c.*10G>C		3_prime_UTR	Exon 18 of 18	NP_001428216.1
	DNMBP	NM_001441288.1		c.*10G>C		3_prime_UTR	Exon 16 of 16	NP_001428217.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.*10G>C		3_prime_UTR	Exon 17 of 17	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000543621.6	TSL:1	c.*10G>C		3_prime_UTR	Exon 14 of 14	ENSP00000443657.2	A0A1C7CYY6
	DNMBP	ENST00000856964.1		c.*10G>C		3_prime_UTR	Exon 18 of 18	ENSP00000527023.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1541 AN: 152080 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00272 AC: 634 AN: 232768 AF XY: 0.00201

Gnomad AFR exome AF: 0.0345

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.000968

Gnomad EAS exome AF: 0.0000600

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00127

GnomAD4 exome AF: 0.00115 AC: 1661 AN: 1445256 Hom.: 24 Cov.: 31 AF XY: 0.00101 AC XY: 722 AN XY: 718064

African (AFR) AF: 0.0363 AC: 1193 AN: 32820

American (AMR) AF: 0.00261 AC: 111 AN: 42490

Ashkenazi Jewish (ASJ) AF: 0.00102 AC: 26 AN: 25442

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38756

South Asian (SAS) AF: 0.0000240 AC: 2 AN: 83438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5694

European-Non Finnish (NFE) AF: 0.000179 AC: 198 AN: 1103792

Other (OTH) AF: 0.00214 AC: 128 AN: 59740

GnomAD4 genome AF: 0.0102 AC: 1554 AN: 152198 Hom.: 33 Cov.: 32 AF XY: 0.00996 AC XY: 741 AN XY: 74416

African (AFR) AF: 0.0352 AC: 1460 AN: 41510

American (AMR) AF: 0.00399 AC: 61 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68018

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00596 Hom.: 1

Bravo AF: 0.0113

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNMBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.48
PhyloP100		0.21
Mutation Taster		=100/0	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: rs2256287; hg19: chr10-101636898;