chr11-7665371-G-GTGTTTGTT

Variant names:

• chr11-7665371-G-GTGTTTGTT
• rs16411
• NM_016229.5:c.*2_*3insAACAAACA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016229.5(CYB5R2):​c.*2_*3insAACAAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,392,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: CYB5R2 NM_016229.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 10 publications found

Genes affected

CYB5R2 (HGNC:24376): (cytochrome b5 reductase 2) The protein encoded by this gene belongs to the flavoprotein pyridine nucleotide cytochrome reductase family of proteins. Cytochrome b-type NAD(P)H oxidoreductases are implicated in many processes including cholesterol biosynthesis, fatty acid desaturation and elongation, and respiratory burst in neutrophils and macrophages. Cytochrome b5 reductases have soluble and membrane-bound forms that are the product of alternative splicing. In animal cells, the membrane-bound form binds to the endoplasmic reticulum, where it is a member of a fatty acid desaturation complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016229.5. 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
	CYB5R2	NM_016229.5	MANE Select	c.*2_*3insAACAAACA		3_prime_UTR	Exon 9 of 9	NP_057313.2
	CYB5R2	NR_126508.2		n.1094_1095insAACAAACA		non_coding_transcript_exon	Exon 10 of 10
	CYB5R2	NM_001302826.2		c.*2_*3insAACAAACA		3_prime_UTR	Exon 9 of 9	NP_001289755.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYB5R2	ENST00000299498.11	TSL:1 MANE Select	c.*2_*3insAACAAACA		3_prime_UTR	Exon 9 of 9	ENSP00000299498.6
	CYB5R2	ENST00000524790.5	TSL:1	c.*232_*233insAACAAACA		3_prime_UTR	Exon 10 of 10	ENSP00000435916.1
	CYB5R2	ENST00000526084.1	TSL:2	n.7196_7197insAACAAACA		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000170 AC: 3 AN: 175990 AF XY: 0.0000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000374

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000718 AC: 10 AN: 1392772 Hom.: 0 Cov.: 40 AF XY: 0.00000874 AC XY: 6 AN XY: 686356

African (AFR) AF: 0.00 AC: 0 AN: 31430

American (AMR) AF: 0.00 AC: 0 AN: 32754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22734

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38518

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51034

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5504

European-Non Finnish (NFE) AF: 0.00000650 AC: 7 AN: 1077430

Other (OTH) AF: 0.00 AC: 0 AN: 57622

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 1860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.054

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16411; hg19: chr11-7686602;