rs4903565

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-77270745-G-A
• chr14-77270745-G-C
• chr14-77270745-G-T

Variant summary

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

The NM_021257.4(NGB):​c.89+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,061,582 control chromosomes in the GnomAD database, including 127,841 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 0.41 (14744 hom., cov: 33)
  • Exomes 𝑓: 0.49 (113097 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 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.89+104C>T		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>T		intron	N/A	ENSP00000298352.4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62877 AN: 152052 Hom.: 14731 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.492 AC: 447251 AN: 909412 Hom.: 113097 AF XY: 0.490 AC XY: 226777 AN XY: 462864

African (AFR) AF: 0.185 AC: 3606 AN: 19480

American (AMR) AF: 0.305 AC: 10048 AN: 32930

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 9630 AN: 20750

East Asian (EAS) AF: 0.453 AC: 13886 AN: 30652

South Asian (SAS) AF: 0.391 AC: 26105 AN: 66694

European-Finnish (FIN) AF: 0.580 AC: 19109 AN: 32932

Middle Eastern (MID) AF: 0.420 AC: 1826 AN: 4350

European-Non Finnish (NFE) AF: 0.521 AC: 343565 AN: 659858

Other (OTH) AF: 0.466 AC: 19476 AN: 41766

GnomAD4 genome AF: 0.413 AC: 62906 AN: 152170 Hom.: 14744 Cov.: 33 AF XY: 0.416 AC XY: 30976 AN XY: 74396

African (AFR) AF: 0.196 AC: 8159 AN: 41550

American (AMR) AF: 0.346 AC: 5294 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2298 AN: 5154

South Asian (SAS) AF: 0.404 AC: 1948 AN: 4824

European-Finnish (FIN) AF: 0.587 AC: 6227 AN: 10612

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.529 AC: 35946 AN: 67954

Other (OTH) AF: 0.415 AC: 876 AN: 2112

Alfa AF: 0.488 Hom.: 2429

Bravo AF: 0.384

Asia WGS AF: 0.436 AC: 1513 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.3
DANN	Benign	0.97
PhyloP100		-0.19
PromoterAI		-0.014	Neutral
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: rs4903565; hg19: chr14-77737088; COSMIC: COSV53612154; COSMIC: COSV53612154;