NM_032207.4:c.-45G>C

Variant names:

• chr19-16496422-G-C
• rs967886
• NM_032207.4:c.-45G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

Genes affected

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

C19orf44 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000141979 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf44	NM_032207.4	MANE Select	c.-45G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_115583.1	Q9H6X5-1
	C19orf44	NM_032207.4	MANE Select	c.-45G>C		5_prime_UTR	Exon 1 of 9	NP_115583.1	Q9H6X5-1
	C19orf44	NM_001288834.2		c.-45G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001275763.1	M0R2B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf44	ENST00000221671.8	TSL:2 MANE Select	c.-45G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000221671.2	Q9H6X5-1
	C19orf44	ENST00000594035.5	TSL:1	c.-45G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000472436.1	M0R2B3
	C19orf44	ENST00000221671.8	TSL:2 MANE Select	c.-45G>C		5_prime_UTR	Exon 1 of 9	ENSP00000221671.2	Q9H6X5-1

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

African (AFR) AF: 0.791 AC: 7053 AN: 8912

American (AMR) AF: 0.876 AC: 11037 AN: 12594

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 8100 AN: 8926

East Asian (EAS) AF: 0.738 AC: 13021 AN: 17636

South Asian (SAS) AF: 0.884 AC: 34247 AN: 38722

European-Finnish (FIN) AF: 0.796 AC: 13610 AN: 17092

Middle Eastern (MID) AF: 0.888 AC: 1085 AN: 1222

European-Non Finnish (NFE) AF: 0.874 AC: 154536 AN: 176858

Other (OTH) AF: 0.859 AC: 14501 AN: 16888

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

African (AFR) AF: 0.794 AC: 32924 AN: 41480

American (AMR) AF: 0.872 AC: 13312 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3572 AN: 5136

South Asian (SAS) AF: 0.886 AC: 4279 AN: 4830

European-Finnish (FIN) AF: 0.770 AC: 8131 AN: 10562

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59054 AN: 68012

Other (OTH) AF: 0.857 AC: 1804 AN: 2104

Alfa AF: 0.829 Hom.: 2632

Bravo AF: 0.838

Asia WGS AF: 0.788 AC: 2740 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.49
PhyloP100		-0.15
PromoterAI		0.24	Neutral
Mutation Taster		=300/0	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: rs967886; hg19: chr19-16607233;