17-64477734-A-G

Position:

• chr17-64477734-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The XM_024450708.2(MILR1):​c.*28+10089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,337,658 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (13 hom.)
• Consequence: MILR1 XM_024450708.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.17

Genes affected

MILR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-64477734-A-G is Benign according to our data. Variant chr17-64477734-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1178761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00727 (1107/152352) while in subpopulation AFR AF= 0.0253 (1054/41580). AF 95% confidence interval is 0.0241. There are 13 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MILR1	XM_024450708.2	c.*28+10089A>G		intron_variant			XP_024306476.2
MILR1	XM_047435791.1	c.*28+10089A>G		intron_variant			XP_047291747.1
MILR1	XR_002957989.2	n.1114+10089A>G		intron_variant, non_coding_transcript_variant
MILR1	XR_002957990.2	n.1114+10089A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1104 AN: 152234 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000678 AC: 804 AN: 1185306 Hom.: 13 AF XY: 0.000549 AC XY: 320 AN XY: 583032

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000961

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00727 AC: 1107 AN: 152352 Hom.: 13 Cov.: 32 AF XY: 0.00717 AC XY: 534 AN XY: 74506

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Bravo AF: 0.00819

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115601318; hg19: chr17-62473851;