chr14-77270745-G-C

Variant names:

• chr14-77270745-G-C
• rs4903565
• NM_021257.4:c.89+104C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021257.4(NGB):​c.89+104C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NGB NM_021257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 4 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.89+104C>G		intron	N/A	NP_067080.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	ENST00000298352.5	TSL:1 MANE Select	c.89+104C>G		intron	N/A	ENSP00000298352.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 911628 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 464006

African (AFR) AF: 0.00 AC: 0 AN: 19512

American (AMR) AF: 0.00 AC: 0 AN: 32968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20778

East Asian (EAS) AF: 0.00 AC: 0 AN: 30684

South Asian (SAS) AF: 0.00 AC: 0 AN: 66760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 661790

Other (OTH) AF: 0.00 AC: 0 AN: 41828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		-0.19
PromoterAI		0.030	Neutral

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: rs4903565; hg19: chr14-77737088;