14-106865837-T-G

Variant names:

• chr14-106865837-T-G
• rs885883
• unassigned_transcript_2645:c.59A>C

Variant summary

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

The ENST00000000000(IGHVII-78-1):​c.59A>C​(p.His20Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGHVII-78-1 ENST00000000000 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 10 publications found

Genes affected

IGHVII-78-1 (HGNC:5691): (immunoglobulin heavy variable (II)-78-1 (pseudogene))

LOC124903399 (HGNC:):

IGH (HGNC:5477):

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=-1.02).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521105.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHVII-78-1	ENST00000521105.1	TSL:6	n.59A>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 11704 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7364

African (AFR) AF: 0.00 AC: 0 AN: 388

American (AMR) AF: 0.00 AC: 0 AN: 628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 248

East Asian (EAS) AF: 0.00 AC: 0 AN: 662

South Asian (SAS) AF: 0.00 AC: 0 AN: 608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 812

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6068

Other (OTH) AF: 0.00 AC: 0 AN: 600

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73816

African (AFR) AF: 0.00 AC: 0 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67408

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 50058

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs885883; hg19: chr14-107274052;