chr17-46297344-A-G

Variant names:

• chr17-46297344-A-G
• rs62073222
• NM_014834.4:c.2211A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014834.4(LRRC37A):​c.2211A>G​(p.Pro737Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,135,268 control chromosomes in the GnomAD database, including 324,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (23199 hom., cov: 18)
  • Exomes 𝑓: 0.70 (324502 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 7 publications found

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 17-46297344-A-G is Benign according to our data. Variant chr17-46297344-A-G is described in ClinVar as Benign. ClinVar VariationId is 403059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 324502 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014834.4. 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
	LRRC37A	NM_014834.4	MANE Select	c.2211A>G	p.Pro737Pro	synonymous	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2182T>C		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2182T>C		intron	N/A	NP_001339698.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.2211A>G	p.Pro737Pro	synonymous	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2211A>G	p.Pro737Pro	synonymous	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2450A>G		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.590 AC: 65820 AN: 111500 Hom.: 23198 Cov.: 18

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.740 AC: 41848 AN: 56530 AF XY: 0.749

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.699

Gnomad EAS exome AF: 0.981

Gnomad FIN exome AF: 0.868

Gnomad NFE exome AF: 0.713

Gnomad OTH exome AF: 0.697

GnomAD4 exome AF: 0.700 AC: 794229 AN: 1135268 Hom.: 324502 Cov.: 27 AF XY: 0.710 AC XY: 407664 AN XY: 574036

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.345 AC: 9703 AN: 28092

American (AMR) AF: 0.714 AC: 23095 AN: 32342

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 15305 AN: 22910

East Asian (EAS) AF: 0.979 AC: 20306 AN: 20750

South Asian (SAS) AF: 0.895 AC: 68710 AN: 76762

European-Finnish (FIN) AF: 0.885 AC: 39619 AN: 44754

Middle Eastern (MID) AF: 0.726 AC: 2507 AN: 3454

European-Non Finnish (NFE) AF: 0.678 AC: 581509 AN: 858066

Other (OTH) AF: 0.695 AC: 33475 AN: 48138

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.590 AC: 65831 AN: 111574 Hom.: 23199 Cov.: 18 AF XY: 0.598 AC XY: 31767 AN XY: 53120

African (AFR) AF: 0.338 AC: 11126 AN: 32934

American (AMR) AF: 0.581 AC: 5519 AN: 9502

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 1875 AN: 2834

East Asian (EAS) AF: 0.950 AC: 1242 AN: 1308

South Asian (SAS) AF: 0.886 AC: 3132 AN: 3534

European-Finnish (FIN) AF: 0.852 AC: 4951 AN: 5814

Middle Eastern (MID) AF: 0.684 AC: 145 AN: 212

European-Non Finnish (NFE) AF: 0.687 AC: 36549 AN: 53170

Other (OTH) AF: 0.589 AC: 931 AN: 1580

Alfa AF: 0.602 Hom.: 2501

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=100/0	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: rs62073222; hg19: chr17-44374710; COSMIC: COSV57225490; COSMIC: COSV57225490;