chr11-7665371-G-GTGTT

Variant names:

• chr11-7665371-G-GTGTT
• rs16411
• NM_016229.5:c.830_*2dupAACA

Variant summary

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

The NM_016229.5(CYB5R2):​c.830_*2dupAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,533,698 control chromosomes in the GnomAD database, including 214,762 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17133 hom., cov: 0)
  • Exomes 𝑓: 0.53 (197629 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

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.830_*2dupAACA		3_prime_UTR	Exon 9 of 9	NP_057313.2
	CYB5R2	NR_126508.2		n.1091_1094dupAACA		non_coding_transcript_exon	Exon 10 of 10
	CYB5R2	NM_001302826.2		c.830_*2dupAACA		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.830_*2dupAACA		3_prime_UTR	Exon 9 of 9	ENSP00000299498.6
	CYB5R2	ENST00000524790.5	TSL:1	c.*229_*232dupAACA		3_prime_UTR	Exon 10 of 10	ENSP00000435916.1
	CYB5R2	ENST00000526084.1	TSL:2	n.7193_7196dupAACA		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70316 AN: 151740 Hom.: 17134 Cov.: 0

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.461

GnomAD2 exomes AF: 0.488 AC: 85892 AN: 175990 AF XY: 0.493

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.454

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.574

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.531 AC: 733366 AN: 1381840 Hom.: 197629 Cov.: 40 AF XY: 0.531 AC XY: 361767 AN XY: 681194

African (AFR) AF: 0.283 AC: 8846 AN: 31306

American (AMR) AF: 0.475 AC: 15435 AN: 32470

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 9207 AN: 22646

East Asian (EAS) AF: 0.640 AC: 24568 AN: 38410

South Asian (SAS) AF: 0.542 AC: 40861 AN: 75322

European-Finnish (FIN) AF: 0.585 AC: 29809 AN: 50950

Middle Eastern (MID) AF: 0.408 AC: 2234 AN: 5478

European-Non Finnish (NFE) AF: 0.537 AC: 573495 AN: 1068010

Other (OTH) AF: 0.505 AC: 28911 AN: 57248

GnomAD4 genome AF: 0.463 AC: 70331 AN: 151858 Hom.: 17133 Cov.: 0 AF XY: 0.467 AC XY: 34668 AN XY: 74210

African (AFR) AF: 0.295 AC: 12221 AN: 41448

American (AMR) AF: 0.472 AC: 7210 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3152 AN: 5148

South Asian (SAS) AF: 0.537 AC: 2589 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6043 AN: 10522

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36145 AN: 67880

Other (OTH) AF: 0.460 AC: 966 AN: 2102

Alfa AF: 0.406 Hom.: 1860

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV55085034; COSMIC: COSV55085034;