14-77266279-CA-C

Variant names:

• chr14-77266279-CA-C
• rs28909969
• NM_021257.4:c.*256delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021257.4(NGB):​c.*256delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 715,338 control chromosomes in the GnomAD database, including 411 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (93 hom., cov: 32)
  • Exomes 𝑓: 0.029 (318 hom.)
• Consequence: NGB NM_021257.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 9 publications found

Genes affected

NGB (HGNC:14077): (neuroglobin) This gene encodes an oxygen-binding protein that is distantly related to members of the globin gene family. It is highly conserved among other vertebrates. It is expressed in the central and peripheral nervous system where it may be involved in increasing oxygen availability and providing protection under hypoxic/ischemic conditions. [provided by RefSeq, Jul 2008]

MIR1260A (HGNC:35325): (microRNA 1260a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021257.4. 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
	NGB	NM_021257.4	MANE Select	c.*256delT		3_prime_UTR	Exon 4 of 4	NP_067080.1
	MIR1260A	NR_031661.1		n.68delA		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	ENST00000298352.5	TSL:1 MANE Select	c.*256delT		3_prime_UTR	Exon 4 of 4	ENSP00000298352.4
	MIR1260A	ENST00000408827.1	TSL:6	n.68delA		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4623 AN: 151938 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0412

GnomAD2 exomes AF: 0.0299 AC: 7451 AN: 248896 AF XY: 0.0305

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.0558

Gnomad EAS exome AF: 0.0159

Gnomad FIN exome AF: 0.0202

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0405

GnomAD4 exome AF: 0.0293 AC: 16510 AN: 563282 Hom.: 318 Cov.: 4 AF XY: 0.0304 AC XY: 9393 AN XY: 308792

African (AFR) AF: 0.0378 AC: 616 AN: 16292

American (AMR) AF: 0.0346 AC: 1436 AN: 41506

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 1074 AN: 18982

East Asian (EAS) AF: 0.0250 AC: 748 AN: 29896

South Asian (SAS) AF: 0.0467 AC: 3195 AN: 68396

European-Finnish (FIN) AF: 0.0209 AC: 968 AN: 46294

Middle Eastern (MID) AF: 0.0663 AC: 247 AN: 3724

European-Non Finnish (NFE) AF: 0.0235 AC: 7259 AN: 309058

Other (OTH) AF: 0.0332 AC: 967 AN: 29134

GnomAD4 genome AF: 0.0304 AC: 4626 AN: 152056 Hom.: 93 Cov.: 32 AF XY: 0.0308 AC XY: 2292 AN XY: 74316

African (AFR) AF: 0.0406 AC: 1683 AN: 41472

American (AMR) AF: 0.0381 AC: 582 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5176

South Asian (SAS) AF: 0.0457 AC: 220 AN: 4812

European-Finnish (FIN) AF: 0.0195 AC: 206 AN: 10566

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1511 AN: 67966

Other (OTH) AF: 0.0403 AC: 85 AN: 2108

Alfa AF: 0.0319 Hom.: 12

Bravo AF: 0.0313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
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: rs28909969; hg19: chr14-77732622; COSMIC: COSV53612056;