19-16496422-G-C

Position:

• chr19-16496422-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032207.4(C19orf44):​c.-45G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 450,926 control chromosomes in the GnomAD database, including 164,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53432 hom., cov: 31)
  • Exomes 𝑓: 0.86 (110917 hom.)
• Consequence: C19orf44 NM_032207.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.155

Genes affected

C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

ENSG00000141979 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-16496422-G-C is Benign according to our data. Variant chr19-16496422-G-C is described in ClinVar as [Benign]. Clinvar id is 1278372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C19orf44	NM_032207.4	c.-45G>C		5_prime_UTR_premature_start_codon_gain_variant	1/9	ENST00000221671.8	NP_115583.1
C19orf44	NM_032207.4	c.-45G>C		5_prime_UTR_variant	1/9	ENST00000221671.8	NP_115583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C19orf44	ENST00000221671	c.-45G>C		5_prime_UTR_premature_start_codon_gain_variant	1/9	2	NM_032207.4	ENSP00000221671.2
C19orf44	ENST00000221671	c.-45G>C		5_prime_UTR_variant	1/9	2	NM_032207.4	ENSP00000221671.2
ENSG00000141979	ENST00000409035.1	n.*380-570C>G		intron_variant		2		ENSP00000386951.2

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127151 AN: 151958 Hom.: 53385 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.861

GnomAD4 exome AF: 0.861 AC: 257190 AN: 298850 Hom.: 110917 Cov.: 2 AF XY: 0.863 AC XY: 136705 AN XY: 158394

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.907

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.859

GnomAD4 genome AF: 0.837 AC: 127255 AN: 152076 Hom.: 53432 Cov.: 31 AF XY: 0.832 AC XY: 61855 AN XY: 74334

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.868

Gnomad4 OTH AF: 0.857

Alfa AF: 0.829 Hom.: 2632

Bravo AF: 0.838

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs967886; hg19: chr19-16607233;